Country：Japan

Country：Japan

Country：Japan

Country：Japan

Country：Japan

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0278013.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.gene.2022.146852

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-022-22166-4

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Publisher：Scientific Reports  

The circadian rhythm is a biological oscillation of physiological activities with a period of approximately 24 h, that is driven by a cell-autonomous oscillator called the circadian clock. The current model of the mammalian circadian clock is based on a transcriptional-translational negative feedback loop in which the protein products of clock genes accumulate in a circadian manner and repress their own transcription. However, several studies have revealed that constitutively expressed clock genes can maintain circadian oscillations. To understand the underlying mechanism, we expressed Bmal1 in Bmal1-disrupted cells using a doxycycline-inducible promoter and monitored Bmal1 and Per2 promoter activity using luciferase reporters. Although the levels of BMAL1 and other clock proteins, REV-ERBα and CLOCK, showed no obvious rhythmicity, robust circadian oscillation in Bmal1 and Per2 promoter activities with the correct phase relationship was observed, which proceeded in a doxycycline-concentration-dependent manner. We applied transient response analysis to the Bmal1 promoter activity in the presence of various doxycycline concentrations. Based on the obtained transfer functions, we suggest that, at least in our experimental system, BMAL1 is not directly involved in the oscillatory process, but modulates the oscillation robustness by regulating basal clock gene promoter activity.

DOI： 10.1038/s41598-022-24188-4

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.cub.2022.09.062

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1371/journal.pone.0257967

DOI： 10.1371/journal.pone.0257967

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Language：English   Publishing type：Research paper (scientific journal)  

Circadian rhythm is an approximately 24 h endogenous biological rhythm. Chronic disruption of the circadian clock leads to an increased risk of diabetes, cardiovascular disease, and cancer. Hence, it is important to develop circadian clock modulators. Natural organisms are a good source of several medicines currently in use. Crude drugs used in Japanese traditional Kampo medicine or folk medicines are an excellent source for drug discovery. Furthermore, identifying new functions for existing drugs, known as the drug repositioning approach, is a popular and powerful tool. In this study, we screened 137 crude drug extracts to act as circadian clock modulators in human U2OS cells stably expressing the clock reporter Bmal1-dLuc, and approximately 12% of these modulated the circadian rhythm. We further examined the effects of several crude drugs in Rat-1 fibroblasts stably expressing Per2-luc, explant culture of lung from Per2::Luciferase knockin mice, and zebrafish larvae in vivo. Notably, more than half of the major ingredients of these crude drugs were reported to target AKT and its relevant signaling pathways. As expected, analysis of the major ingredients targeting AKT signaling confirmed the circadian clock-modulating effects. Furthermore, activator and inhibitor of AKT, and triple knockdown of AKT isoforms by siRNA also modulated the circadian rhythm. This study, by employing the drug repositioning approach, shows that Kampo medicines are a useful source for the identification of underlying mechanisms of circadian clock modulators and could potentially be used in the treatment of circadian clock disruption.

DOI： 10.1038/s41598-021-00499-w

DOI： 10.1038/s41598-021-00499-w

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The circadian clock controls daily rhythms of various physiological processes, and impairment of its function causes many diseases including sleep disorders. Chemical compounds that regulate clock function are expected to be applied for treatment of circadian clock-related diseases. We previously identified small-molecule compounds KL001, KL101, and TH301 that lengthen the period of cellular circadian clock by directly targeting clock proteins Cryptochromes (CRYs) in mammals. KL001 targets both CRY1 and CRY2 isoforms, while KL101 and TH301 are isoform-selective compounds and require CRY C-terminal region for their effects. For further application of these compounds, the effects on locomotor activity rhythms at the organismal level need to be investigated. Here we used zebrafish larvae as an in vivo model system and found that KL001 lengthened the period of locomotor activity rhythms in a dose-dependent manner. In contrast, KL101 and TH301 showed no effect on the period. The amino acid sequences of CRY C-terminal regions are diverged in zebrafish and mammals, supporting the importance of this region for the effects of KL101 and TH301. This study demonstrated efficacy of CRY modulation for controlling circadian behavioral rhythms in organisms and suggested species-dependent differences in the effects of isoform-selective CRY-modulating compounds.

DOI： 10.1093/jb/mvab096

DOI： 10.1093/jb/mvab096

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PubMed

Authorship：Last author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

At high latitudes, approximately 10% of people suffer from depression during the winter season, a phenomenon known as seasonal affective disorder (SAD). Shortened photoperiod and/or light intensity during winter season are risk factors for SAD, and bright light therapy is an effective treatment. Interestingly, reduced retinal photosensitivity along with the mood is observed in SAD patients in winter. However, the molecular basis underlying seasonal changes in retinal photosensitivity remains unclear, and pharmacological intervention is required. Here we show photoperiodic regulation of dopamine signaling and improvement of short day-attenuated photosensitivity by its pharmacological intervention in mice. Electroretinograms revealed dynamic seasonal changes in retinal photosensitivity. Transcriptome analysis identified short day-mediated suppression of the Th gene, which encodes tyrosine hydroxylase, a rate-limiting enzyme for dopamine biosynthesis. Furthermore, pharmacological intervention in dopamine signaling through activation of the cAMP signaling pathway rescued short day-attenuated photosensitivity, whereas dopamine receptor antagonists decreased photosensitivity under long-day conditions. Our results reveal molecular basis of seasonal changes in retinal photosensitivity in mammals. In addition, our findings provide important insights into the pathogenesis of SAD and offer potential therapeutic interventions.

DOI： 10.1038/s41598-021-81540-w

DOI： 10.1038/s41598-021-81540-w

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PubMed

Publisher：Endocrinology (United States)  

Organisms that inhabit the temperate zone exhibit various seasonal adaptive behaviors, including reproduction, hibernation, molting, and migration. Day length, known as photoperiod, is the most noise-free and widely used environmental cue that enables animals to anticipate the oncoming seasons and adapt their physiologies accordingly. Although less clear, some human traits also exhibit seasonality, such as birthrate, mood, cognitive brain responses, and various diseases. However, the molecular basis for human seasonality is poorly understood. Herein, we first review the underlying mechanisms of seasonal adaptive strategies of animals, including seasonal reproduction and stress responses during the breeding season. We then briefly summarize our recent discovery of signaling pathways involved in the winter depression-like phenotype in medaka fish. We believe that exploring the regulation of seasonal traits in animal models will provide insight into human seasonality and aid in the understanding of human diseases such as seasonal affective disorder (SAD).

DOI： 10.1210/endocr/bqaa130

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Language：English   Publishing type：Research paper (scientific journal)  

The genetic bases of growth and body weight are of economic and scientific interest, and teleost fish models have proven useful in such investigations. The Oryzias latipes species complex (medaka) is an abundant freshwater fish in Japan and suitable for genetic studies. We compared two wild medaka stocks originating from different latitudes. The Maizuru population from higher latitudes weighed more than the Ginoza population. We investigated the genetic basis of body weight, using quantitative trait locus (QTL) analysis of the F2 offspring of these populations. We detected one statistically significant QTL for body weight on medaka chromosome 4 and identified 12 candidate genes that might be associated with body weight or growth. Nine of these 12 genes had at least one single nucleotide polymorphism that caused amino acid substitutions in protein-coding regions, and we estimated the effects of these substitutions. The present findings might contribute to the marker-assisted selection of economically important aquaculture species.

DOI： 10.1371/journal.pone.0234803

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Language：Japanese   Publisher：Evolution Letters  

The trade-off between reproduction and self-maintenance is a cornerstone of life history theory, yet its proximate underpinnings are elusive. Here, we used an artificial selection approach to create replicated lines of Japanese quail (Coturnix japonica) that differ genetically in their reproductive investment. Whole transcriptome sequencing revealed that females from lines selected for high reproductive output show a consistent upregulation of genes associated with reproduction but a simultaneous downregulation of immune genes. Concordant phenotypic differences in immune function (i.e., specific antibody response against keyhole limpet hemocyanin) were observed between the selection lines, even in males who do not provide parental care. Our findings demonstrate the key role of obligate transcriptional constraints in the maintenance of life history variation. These constraints set fundamental limits to productivity and health in natural and domestic animal populations.

DOI： 10.1002/evl3.166

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Language：English   Publishing type：Research paper (scientific journal)  

Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like conditions. Whole brain metabolomic analysis revealed seasonal changes in 68 metabolites, including neurotransmitters and antioxidants associated with depression. Transcriptome analysis identified 3,306 differentially expressed transcripts, including inflammatory markers, melanopsins, and circadian clock genes. Further analyses revealed seasonal changes in multiple signaling pathways implicated in depression, including the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway. A broad-spectrum chemical screen revealed that celastrol (a traditional Chinese medicine) uniquely reversed winter behavior. NRF2 is a celastrol target expressed in the habenula (HB), known to play a critical role in the pathophysiology of depression. Another NRF2 chemical activator phenocopied these effects, and an NRF2 mutant showed decreased sociability. Our study provides important insights into winter depression and offers potential therapeutic targets involving NRF2.

DOI： 10.1073/pnas.2000278117

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PubMed

Publisher：BMC Biology  

Background: The Japanese quail (Coturnix japonica) is a popular domestic poultry species and an increasingly significant model species in avian developmental, behavioural and disease research. Results: We have produced a high-quality quail genome sequence, spanning 0.93 Gb assigned to 33 chromosomes. In terms of contiguity, assembly statistics, gene content and chromosomal organisation, the quail genome shows high similarity to the chicken genome. We demonstrate the utility of this genome through three diverse applications. First, we identify selection signatures and candidate genes associated with social behaviour in the quail genome, an important agricultural and domestication trait. Second, we investigate the effects and interaction of photoperiod and temperature on the transcriptome of the quail medial basal hypothalamus, revealing key mechanisms of photoperiodism. Finally, we investigate the response of quail to H5N1 influenza infection. In quail lung, many critical immune genes and pathways were downregulated after H5N1 infection, and this may be key to the susceptibility of quail to H5N1. Conclusions: We have produced a high-quality genome of the quail which will facilitate further studies into diverse research questions using the quail as a model avian species.

DOI： 10.1186/s12915-020-0743-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media {LLC}  

Circadian rhythmicity is an approximately 24-h cell-autonomous period driven by transcription-translation feedback loops of specific genes, which are referred to as 'circadian clock genes'. In mammals, the central circadian pacemaker, which is located in the hypothalamic suprachiasmatic nucleus, controls peripheral circadian clocks. The circadian system regulates virtually all physiological processes, which are further modulated by changes in the external environment, such as light exposure and the timing of food intake. Chronic circadian disruption caused by shift work, travel across time zones or irregular sleep-wake cycles has long-term consequences for our health and is an important lifestyle factor that contributes to the risk of obesity, type 2 diabetes mellitus and cancer. Although the hypothalamic-pituitary-thyroid axis is under the control of the circadian clock via the suprachiasmatic nucleus pacemaker, daily TSH secretion profiles are disrupted in some patients with hypothyroidism and hyperthyroidism. Disruption of circadian rhythms has been recognized as a perturbation of the endocrine system and of cell cycle progression. Expression profiles of circadian clock genes are abnormal in well-differentiated thyroid cancer but not in the benign nodules or a healthy thyroid. Therefore, the characterization of the thyroid clock machinery might improve the preoperative diagnosis of thyroid cancer.

DOI： 10.1038/s41574-019-0237-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

DOI： 10.1371/journal.pone.0222106

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Publisher：Proceedings of the Japan Academy Series B: Physical and Biological Sciences  

Animals make use of changes in photoperiod to adapt their physiology to the forthcoming breeding season. Comparative studies have contributed to our understanding of the mechanisms of seasonal reproduction in vertebrates. Birds are excellent models for studying these phenomena because of their rapid and dramatic responses to changes in photoperiod. Deep brain photoreceptors in birds perceive and transmit light information to the pars tuberalis (PT) in the pituitary gland, where the thyroid-stimulating hormone (TSH) is produced. This PT-TSH locally increases the level of the bioactive thyroid hormone T3 via the induction of type 2 deiodinase production in the mediobasal hypothalamus, and an increased T3 level, in turn, controls seasonal gonadotropin-releasing hormone secretion. In mammals, the eyes are the only photoreceptive structure, and nocturnal melatonin secretion encodes day-length information and regulates the PTTSH signaling cascade. In Salmonidae, the saccus vasculosus plays a pivotal role as a photoperiodic sensor. Together, these studies have uncovered the universality and diversity of fundamental traits in vertebrates.

DOI： 10.2183/pjab.95.025

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Language：English   Publishing type：Research paper (scientific journal)  

The circadian clock provides organisms with the ability to adapt to daily and seasonal cycles. Eukaryotic clocks mostly rely on lineage-specific transcriptional-translational feedback loops (TTFLs). Posttranslational modifications are also crucial for clock functions in fungi and animals, but the posttranslational modifications that affect the plant clock are less understood. Here, using chemical biology strategies, we show that the Arabidopsis CASEIN KINASE 1 LIKE (CKL) family is involved in posttranslational modification in the plant clock. Chemical screening demonstrated that an animal CDC7/CDK9 inhibitor, PHA767491, lengthens the Arabidopsis circadian period. Affinity proteomics using a chemical probe revealed that PHA767491 binds to and inhibits multiple CKL proteins, rather than CDC7/CDK9 homologs. Simultaneous knockdown of Arabidopsis CKL-encoding genes lengthened the circadian period. CKL4 phosphorylated transcriptional repressors PSEUDO-RESPONSE REGULATOR 5 (PRR5) and TIMING OF CAB EXPRESSION 1 (TOC1) in the TTFL. PHA767491 treatment resulted in accumulation of PRR5 and TOC1, accompanied by decreasing expression of PRR5- and TOC1-target genes. A prr5 toc1 double mutant was hyposensitive to PHA767491-induced period lengthening. Together, our results reveal posttranslational modification of transcriptional repressors in plant clock TTFL by CK1 family proteins, which also modulate nonplant circadian clocks.

DOI： 10.1073/pnas.1903357116

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41559-019-0866-6

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Other Link： http://www.nature.com/articles/s41559-019-0866-6

Language：Japanese   Publisher：Scientific Reports  

Animals that communicate using sound are found throughout the animal kingdom. Interestingly, in contrast to human vocal learning, most animals can produce species-specific patterns of vocalization without learning them from their parents. This phenomenon is called innate vocalization. The underlying molecular basis of both vocal learning in humans and innate vocalization in animals remains unknown. The crowing of a rooster is also innately controlled, and the upstream center is thought to be localized in the nucleus intercollicularis (ICo) of the midbrain. Here, we show that the cholecystokinin B receptor (CCKBR) is a regulatory gene involved in inducing crowing in roosters. Crowing is known to be a testosterone (T)-dependent behavior, and it follows that roosters crow but not hens. Similarly, T-administration induces chicks to crow. By using RNA-sequencing to compare gene expression in the ICo between the two comparison groups that either crow or do not crow, we found that CCKBR expression was upregulated in T-containing groups. The expression of CCKBR and its ligand, cholecystokinin (CCK), a neurotransmitter, was observed in the ICo. We also showed that crowing was induced by intracerebroventricular administration of an agonist specific for CCKBR. Our findings therefore suggest that the CCK system induces innate vocalization in roosters.

DOI： 10.1038/s41598-019-40746-9

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Language：English   Publishing type：Research paper (scientific journal)  

Masking is a direct behavioral response to environmental changes and plays an important role in the temporal distribution of activity. However, the mechanisms responsible for masking remain unclear. Here we identify thermosensors and a possible neural circuit regulating temperature-dependent masking behavior in mice. Analysis of mice lacking thermosensitive transient receptor potential (TRP) channels (Trpv1/3/4 and Trpm2/8) reveals that temperature-dependent masking is impaired in Trpm2- and Trpm8-null mice. Several brain regions are activated during temperature-dependent masking, including the preoptic area (POA), known as the thermoregulatory center, the suprachiasmatic nucleus (SCN), which is the primary circadian pacemaker, the paraventricular nucleus of the thalamus (PVT), and the nucleus accumbens (NAc). The POA, SCN, PVT are interconnected, and the PVT sends dense projections to the NAc, a key brain region involved in wheel-running activity. Partial chemical lesion of the PVT attenuates masking, suggesting the involvement of the PVT in temperature-dependent masking behavior.

DOI： 10.1038/s41598-019-40067-x

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Organisms use changes in photoperiod for seasonal reproduction to maximize the survival of their offspring. Birds have sophisticated seasonal mechanisms and are therefore excellent models for studying these phenomena. Birds perceive light via deep-brain photoreceptors and long day-induced thyroid-stimulating hormone (TSH, thyrotropin) in the pars tuberalis of the pituitary gland (PT), which cause local thyroid hormone activation within the mediobasal hypothalamus. The local bioactive thyroid hormone controls seasonal gonadotropin-releasing hormone secretion and subsequent gonadotropin secretion. In mammals, the eyes are believed to be the only photoreceptor organ, and nocturnal melatonin secretion triggers an endocrine signal that communicates information about the photoperiod to the PT to regulate TSH. In contrast, in Salmonidae fish the input pathway to the neuroendocrine output pathway appears to be localized in the saccus vasculosus. Thus, comparative analysis is an effective way to uncover the universality and diversity of fundamental traits in various organisms.

DOI： 10.1146/annurev-animal-020518-115216

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PubMed

Authorship：Corresponding author  

Authorship：Lead author,　Corresponding author  

Authorship：Lead author,　Corresponding author  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.isci.2018.08.010

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Academic Press Inc.  

In temperate zones, organisms experience dynamic fluctuations in environment including changes in color. To cope with such seasonal changes in the environment, organisms adapt their physiology and behavior. Although color perception has been believed to be fixed throughout life, there is increasing evidence for the alteration in opsin gene expression induced by environmental stimuli in a number of animals. Very recently, dynamic seasonal plasticity in color perception has been reported in the seasonally breeding medaka fish. Interestingly, seasonal changes in human color perception have also been reported. Therefore, plasticity of color perception, induced by environmental stimuli, might be a common phenomenon across various species.

DOI： 10.1016/j.ygcen.2017.12.010

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Language：Japanese  

DOI： 10.1016/j.ygcen.2018.03.002

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Language：English   Publishing type：Research paper (scientific journal)  

Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time-consuming. We therefore performed a high-throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period-shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA Dietary administration of DHEA to mice shortened free-running circadian period and accelerated re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders.

DOI： 10.15252/emmm.201708724

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1089/thy.2017.0186

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/978-4-431-56609-0_6

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Authorship：Last author,　Corresponding author  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

To cope with seasonal changes in the environment, organisms adapt their physiology and behavior. Although color perception varies among seasons, the underlying molecular basis and its physiological significance remain unclear. Here we show that dynamic plasticity in phototransduction regulates seasonal changes in color perception in medaka fish. Medaka are active and exhibit clear phototaxis in conditions simulating summer, but remain at the bottom of the tank and fail to exhibit phototaxis in conditions simulating winter. Mate preference tests using virtual fish created with computer graphics demonstrate that medaka are more attracted to orange-red-colored model fish in summer than in winter. Transcriptome analysis of the eye reveals dynamic seasonal changes in the expression of genes encoding photopigments and their downstream pathways. Behavioral analysis of photopigment-null fish shows significant differences from wild type, suggesting that plasticity in color perception is crucial for the emergence of seasonally regulated behaviors.

DOI： 10.1038/s41467-017-00432-8

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Language：English   Publishing type：Research paper (scientific journal)  

Thyroid hormones (TH) are important for development, growth, and metabolism. It is also clear that the synthesis and secretion of TH are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our understanding of the roles and regulatory mechanisms of TH. The animals' bodies develop through coordinated timing of cell division and differentiation. Studies of frog metamorphosis led to the discovery of TH and their role in development. However, to adapt to rhythmic environmental changes, animals also developed various endocrine rhythms. Studies of rodents clarified the neural and molecular mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds have a sophisticated seasonal adaptation mechanism, and recent studies of quail revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the seasonal regulation of reproduction. Interestingly, this mechanism is conserved in mammals. Thus, we review how animal studies have shaped our general understanding of the HPT axis in relation to biological rhythms.

DOI： 10.1016/j.beem.2017.09.002

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Language：English   Publishing type：Part of collection (book)   Publisher：Springer (India) Private Ltd.  

The mechanisms of vertebrate seasonal time measurement were a mystery for a long time, but recent comparative studies have uncovered the photoperiodic signal transduction cascades in birds, mammals, and fish. These studies reveal the universality and diversity of photoperiodic mechanisms. That is, the molecules involved are conserved, while the tissues responsible for these mechanisms are different in different species (Nakane and Yoshimura, Front Neurosci 8:115, 2014). It is well established that the circadian clock is involved in photoperiodic time measurement. However, the underlying mechanism that defines the photoinducible phase or critical photoperiod (i.e., how organisms measure day length using a circadian clock) is at the heart of photoperiodic time measurement, and this question remains to be answered by future studies.

DOI： 10.1007/978-81-322-3688-7_28

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Language：English   Publishing type：Part of collection (book)   Publisher：Springer New York LLC  

Animals living outside tropical zones experience seasonal changes in the environment and accordingly, adapt their physiology and behavior in reproduction, molting, and migration. Subtropical birds are excellent models for the study of seasonal reproduction because of their rapid and dramatic response to changes in photoperiod. For example, testicular weight typically changes by more than a 100-fold. In birds, the eyes are not necessary for seasonal reproduction, and light is instead perceived by deep brain photoreceptors. Functional genomic analysis has revealed that long day (LD)-induced thyrotropin from the pars tuberalis of the pituitary gland causes local thyroid hormone (TH) activation within the mediobasal hypothalamus. This local bioactive TH, triiodothyronine (T3), appears to regulate seasonal gonadotropin-releasing hormone (GnRH) secretion through morphological changes in neuro-glial interactions. GnRH, in turn, stimulates gonadotropin secretion and hence, gonadal development under LD conditions. In marked contrast, low temperatures accelerate short day (SD)-induced testicular regression in winter. Interestingly, low temperatures increase circulating levels of T3 to support adaptive thermogenesis, but this induction of T3 also triggers the apoptosis of germ cells by activating genes involved in metamorphosis. This apparent contradiction in the role of TH has recently been clarified. Central activation of TH during spring results in testicular growth, while peripheral activation of TH during winter regulates adaptive thermogenesis and testicular regression.

DOI： 10.1007/978-981-10-3975-1_8

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1530/JOE-16-0066

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Language：English   Publishing type：Research paper (scientific journal)  

Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms.

DOI： 10.1016/j.ygcen.2015.05.009

DOI： 10.1016/j.ygcen.2015.05.009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Poultry Science Association  

Organisms measure day length to better adapt to seasonal changes in the environment; this phenomenon is called photoperiodism. The Japanese quail has a highly sophisticated photoperiodic mechanism and is an excellent model for the study of photoperiodism. Various lines of quail have been established during the domestication process. In the present study, we examined the effect of long day (LD) followed by short day (SD) on testicular weight in four lines of quail (L, AMRP, NIES-Br, and WE). When the quail were raised under SD conditions, testicular development was suppressed in all examined lines. The speed of the LD-induced testicular development of NIES-Br line was faster than that of AMRP line, while the speed of the SD-induced testicular regression of L line was significantly faster than that of WE line. These quail lines provide excellent model to uncover the underlying mechanism of seasonal testicular regression.

DOI： 10.2141/jpsa.0150097

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CiNii Books

Other Link： https://jlc.jst.go.jp/DN/JLC/20019782070?from=CiNii

Authorship：Last author,　Corresponding author  

Authorship：Last author,　Corresponding author  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Although successful fertilization depends on timely encounters between sperm and egg, the decoupling of mating and fertilization often confers reproductive advantages to internally fertilizing animals. In several vertebrate groups, postcopulatory sperm viability is prolonged by storage in specialized organs within the female reproductive tract. In birds, ejaculated sperm can be stored in a quiescent state within oviductal sperm storage tubules (SSTs), thereby retaining fertilizability for up to 15 weeks at body temperature (41 degrees C); however, the mechanism by which motile sperm become quiescent within SSTs is unknown. Here, we show that low oxygen and high lactic acid concentrations are established in quail SSTs. Flagellar quiescence was induced by lactic acid in the concentration range found in SSTs through flagellar dynein ATPase inactivation following cytoplasmic acidification (<pH 6.0). The long-term preservation of sperm morphology under hypoxic and high temperature conditions indicates that a combination of these factors enables sperm cells to survive during the ovulation cycles. Our findings suggested a novel physiological role for lactic acid in promoting sperm quiescence in SSTs and opened up a new opportunity for technological improvement in prolonging sperm longevity at ambient or body temperature.

DOI： 10.1038/srep17643

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DOI： 10.1210/en.2015-1415

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DOI： 10.1098/rspb.2015.1453

DOI： 10.1098/rspb.2015.1453

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

The "cock-a-doodle-doo" crowing of roosters, which symbolizes the break of dawn in many cultures, is controlled by the circadian clock. When one rooster announces the break of dawn, others in the vicinity immediately follow. Chickens are highly social animals, and they develop a linear and fixed hierarchy in small groups. We found that when chickens were housed in small groups, the top-ranking rooster determined the timing of predawn crowing. Specifically, the top-ranking rooster always started to crow first, followed by its subordinates, in descending order of social rank. When the top-ranking rooster was physically removed from a group, the second-ranking rooster initiated crowing. The presence of a dominant rooster significantly reduced the number of predawn crows in subordinates. However, the number of crows induced by external stimuli was independent of social rank, confirming that subordinates have the ability to crow. Although the timing of subordinates' predawn crowing was strongly dependent on that of the top-ranking rooster, free-running periods of body temperature rhythms differed among individuals, and crowing rhythm did not entrain to a crowing sound stimulus. These results indicate that in a group situation, the top-ranking rooster has priority to announce the break of dawn, and that subordinate roosters are patient enough to wait for the top-ranking rooster's first crow every morning and thus compromise their circadian clock for social reasons.

DOI： 10.1038/srep11683

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DOI： 10.1002/anie.201502942

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DOI： 10.1210/en.2014-1741

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Fertilization is an indispensable step for formation of a zygote in sexual reproduction, leading to species survival. When mating occurs, sperm is transported to the female reproductive tracts via the seminal plasma (SP). SP is derived from male accessory sex glands and it plays pivotal roles for fertilization in animals. However, molecular mechanisms of SP or a fluid derived from male accessory sex glands for successful fertilization remain unclear. Here, we report that in male quail the cloacal gland (CG) produces prostaglandin F-2 alpha (PGF(2 alpha)) that contributes to successful fertilization. PGF(2 alpha), as well as the secretion of CG (CGS), induced vaginal contractions and caused the opening of the entrance of the sperm storage tubules, the structures responsible for the long-term sperm storage and fertilization. The removal of CGS from the male before mating reduced the fertility, but the supplementation of CGS or PGF(2 alpha) rescued the subfertility. We further showed that male CG contains glucose that is utilized as energy source for the intrinsic sperm mobility after transportation to female vagina. This mechanism, in concert with the excitatory effects of PGF(2 alpha) enables successful fertilization in the domestic bird.

DOI： 10.1038/srep07700

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本神経精神薬理学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Comparative Endocrinology  

DOI： 10.5983/nl2008jsce.41.127

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Authorship：Last author,　Corresponding author  

DOI： 10.1016/j.cub.2014.10.021

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Attention deficit/hyperactivity disorder (ADHD) has been reported in association with resistance to thyroid hormone, a disease caused by a mutation in the thyroid hormone receptor β (TRβ) gene. TRβ is a key protein mediating down-regulation of thyrotropin (TSH) expression by 3,3',5-tri-iodothyronine (T3), an active form of thyroid hormone. Dysregulation of TSH and its receptor (TSHR) is implicated in the pathophysiology of ADHD but the role of TSHR remains elusive. Here, we clarified a novel role for TSHR in emotional and cognitive functions related to monoaminergic nervous systems. TSHR knockout mice showed phenotypes of ADHD such as hyperactivity, impulsiveness, a decrease in sociality and increase in aggression, and an impairment of short-term memory and object recognition memory. Administration of methylphenidate (1, 5 and 10mg/kg) reversed impulsiveness, aggression and object recognition memory impairment. In the knockout mice, monoaminergic changes including decrease in the ratio of 3-methoxy-4-hydroxyphenylglycol/noradrenaline and increase in the ratio of homovanillic acid/dopamine were observed in some brain regions, accompanied by increase in the expression of noradrenaline transporter in the frontal cortex. When TSH was completely suppressed by the supraphysiological administration of T3 to the adult mice, some behavioral and neurological changes in TSHR KO mice were also observed, suggesting that these changes were not due to developmental hypothyroidism induced by the inactivation of TSHR but to the loss of the TSH-TSHR pathway itself. Taken together, the present findings suggest a novel role for TSHR in behavioral and neurological phenotypes of ADHD.

DOI： 10.1016/j.psyneuen.2014.05.021

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PubMed

Language：English   Publisher：CELL PRESS  

DOI： 10.1016/j.cub.2014.05.038

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Scopus

Language：English   Publisher：FRONTIERS RESEARCH FOUNDATION  

Most vertebrates living outside the tropical zone show robust physiological responses in response to seasonal changes in photoperiod, such as seasonal reproduction, molt, and migration. The highly sophisticated photoperiodic mechanism in Japanese quail has been used to uncover the mechanism of seasonal reproduction. Molecular analysis of quail mediobasal hypothalamus (MBH) revealed that local thyroid hormone activation within the MBH plays a critical role in the photoperiodic response of gonads. This activation is accomplished by two gene switches: thyroid hormone-activating (DIO2) and thyroid hormone-inactivating enzymes (DIO3). Functional genomics studies have shown that long-day induced thyroid-stimulating hormone (TSH) in the pars tuberalis (PT) of the pituitary gland regulates DIO2/3 switching. In birds, light information received directly by deep brain photoreceptors regulates PT TSH. Recent studies demonstrated that Opsin 5-positive cerebrospinal fluid (CSF)-contacting neurons are deep brain photoreceptors that regulate avian seasonal reproduction. Although the involvement of TSH and DIO2/3 in seasonal reproduction has been confirmed in various mammals, the light input pathway that regulates PT TSH in mammals differs from that of birds. In mammals, the eye is the only photoreceptor organ and light information received by the eye is transmitted to the pineal gland through the circadian pacemaker, the suprachiasmatic nucleus. Nocturnal melatonin secretion from the pineal gland indicates the length of night and regulates the PT TSH. In fish, the regulatory machinery for seasonal reproduction, from light input to neuroendocrine output, has been recently demonstrated in the coronet cells of the saccus vasculosus (SV). The SV is unique to fish and coronet cells are CSF-contacting neurons. Here, we discuss the universality and diversity of signal transduction pathways that regulate vertebrate seasonal reproduction.

DOI： 10.3389/fnins.2014.00115

DOI： 10.3389/fnins.2014.00115

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Language：English   Publishing type：Research paper (scientific journal)  

Systems for maintaining the viability of ejaculated sperm in the female reproductive tract are widespread among vertebrates and invertebrates. In birds, this sperm storage function is performed by specialized simple tubular invaginations called sperm storage tubules (SSTs) in the uterovaginal junction (UVJ) of the oviduct. Although the incidence and physiological reasons for sperm storage in birds have been reported extensively, the mechanisms of sperm uptake by the SSTs, sperm maintenance within the SSTs, and control of sperm release from the SSTs are poorly understood. In this study, we demonstrated that the highly conserved heat shock protein 70 (HSP70) stimulates sperm motility in vitro and also that HSP70 expressed in the UVJ may facilitate the migration of sperm released from the SSTs. Quantitative RT-PCR analysis demonstrated that the expression of HSP70 mRNA in the UVJ increases before ovulation/oviposition. Gene-specific in situ hybridization and immunohistochemical analysis with a specific antibody to HSP70 demonstrated that HSP70 is localized in the surface epithelium of the UVJ. Furthermore, injection of anti-HSP70 antibody into the vagina significantly inhibited fertilization in vivo. In addition, we found that recombinant HSP70 activates flagellar movement in the sperm and that the binding of recombinant HSP70 to the sperm surface is mediated through an interaction with voltage-dependent anion channel protein 2 (VDAC2). Our results suggest that HSP70 binds to the sperm surface by interacting with VDAC2 and activating sperm motility. This binding appears to play an important role in sperm migration within the oviduct.

DOI： 10.1530/REP-13-0439

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PubMed

Language：Japanese   Publisher：Japan Society for Comparative Endocrinology  

DOI： 10.5983/nl2008jsce.40.65

CiNii Books

Language：English   Publishing type：Research paper (scientific journal)  

Organisms living outside the tropics measure the changes in the length of the day to adapt to seasonal changes in the environment. Animals that breed during spring and summer are called long-day breeders, while those that breed during fall are called short-day breeders. Although the influence of thyroid hormone in the regulation of seasonal reproduction has been known for several decades, its precise mechanism remained unknown. Recent studies revealed that the activation of thyroid hormone within the mediobasal hypothalamus plays a key role in this phenomenon. This localized activation of the thyroid hormone is controlled by thyrotropin (thyroid-stimulating hormone) secreted from the pars tuberalis of the pituitary gland. Although seasonal reproduction is a rate-limiting factor in animal production, genes involved in photoperiodic signal transduction pathway could emerge as potential targets to facilitate domestication.

DOI： 10.3389/fendo.2014.00012

DOI： 10.3389/fendo.2014.00012

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PubMed

Authorship：Last author,　Corresponding author  

Language：English   Publishing type：Research paper (scientific journal)  

The mammalian circadian oscillator is composed of interacting positive and negative transcription events. The clock proteins PER1 and PER2 play essential roles in a negative limb of the feedback loop that generates the circadian rhythm in mammals. In addition, the proteins CLOCK and BMAL1 (also known as ARNTL) form a heterodimer that drives the Per genes via the E-box consensus sequences within their promoter regions. In the present study, we demonstrate that Id2 is involved in stabilization of the amplitudes of the circadian oscillations by suppressing transcriptional activation of clock genes Clock and Bmal1. Id2 shows dynamic oscillation in the SCN, with a peak in the late subjective night. Under constant dark conditions (DD), Id2(-/-) mice showed no apparent difference in locomotor activity, however, under constant light conditions (LL), Id2(-/-) mice exhibit aberrant locomotor activity, with lower circadian oscillation amplitudes, although the free running periods in Id2(-/-) mice show no differences from those in either wild type or heterozygous mice. Id2(-/-) animals also exhibit upregulation of Per1 in constant light, during both the subjective night and day. In wild type mice, Id2 is upregulated by constant light exposure during the subjective night. We propose that Id2 expression in the SCN contributes to maintenance of dynamic circadian oscillations.

DOI： 10.2108/zsj.30.1011

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DOI： 10.1016/j.yfrne.2013.04.002

DOI： 10.1016/j.yfrne.2013.04.002

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Language：English   Publishing type：Research paper (scientific journal)  

Most species living outside the tropical zone undergo physiological adaptations to seasonal environmental changes and changing day length (photoperiod); this phenomenon is called photoperiodism. It is well known that the circadian clock is involved in the regulation of photoperiodism such as seasonal reproduction, but the mechanism underlying circadian clock regulation of photoperiodism remains unclear. Recent molecular analysis have revealed that, in mammals and birds, the pars tuberalis (PT) of the pituitary gland acts as the relay point from light receptors, which receive information about the photoperiod, to the endocrine responses. Long-day (LD)-induced thyroid-stimulating hormone (TSH) in the PT acts as a master regulator of seasonal reproduction in the ependymal cells (ECs) within the mediobasal hypothalamus (MBH) and activates thyroid hormone (TH) by inducing the expression of type 2 deiodinase in both LD and short-day (SD) breeding animals. Furthermore, the circadian clock has been found to be localized in the PT and ECs as well as in the circadian pacemaker(s). This review purposes to summarize the current knowledge concerning the involvement of the neuroendocrine system and circadian clock in seasonal reproduction.

DOI： 10.1262/jrd.2013-035

DOI： 10.1262/jrd.2013-035

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PubMed

DOI： 10.1038/ncomms3108

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

The Japanese quail has several advantages as a laboratory animal for biological and biomedical investigations. In this study, the draft genome of the Japanese quail was sequenced and assembled using next-generation sequencing technology. To improve the quality of the assembly, the sequence reads from the Japanese quail were aligned against the reference genome of the chicken. The final draft assembly consisted of 1.75 Gbp with an N50 contig length of 11,409 bp. On the basis of the draft genome sequence obtained, we developed 100 microsatellite markers and used these markers to evaluate the genetic variability and diversity of 11 lines of Japanese quail. Furthermore, we identified Japanese quail orthologs of spermatogenesis markers and analyzed their expression using in situ hybridization. The Japanese quail genome sequence obtained in the present study could enhance the value of this species as a model animal. (C) 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ygeno.2013.03.006

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PubMed

Other Link： http://orcid.org/0000-0003-2072-8851

Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

DOI： 10.1016/j.cub.2013.02.015

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Language：English   Publishing type：Research paper (scientific journal)  

In mammals, light information received by the eyes is transmitted to the pineal gland via the circadian pacemaker, i.e., the suprachiasmatic nucleus (SCN). Melatonin secreted by the pineal gland at night decodes night length and regulates seasonal physiology and behavior. Melatonin regulates the expression of the β-subunit of thyroid-stimulating hormone (TSH; Tshb) in the pars tuberalis (PT) of the pituitary gland. Long day-induced PT TSH acts on ependymal cells in the mediobasal hypothalamus to induce the expression of type 2 deiodinase (Dio2) and reduce type 3 deiodinase (Dio3) that are thyroid hormone-activating and hormone-inactivating enzymes, respectively. The long day-activated thyroid hormone T3 regulates seasonal gonadotropin-releasing hormone secretion. It is well established that the circadian clock is involved in the regulation of photoperiodism. However, the involvement of the circadian clock gene in photoperiodism regulation remains unclear. Although mice are generally considered non-seasonal animals, it was recently demonstrated that mice are a good model for the study of photoperiodism. In the present study, therefore, we examined the effect of changing day length in Per2 deletion mutant mice that show shorter wheel-running rhythms under constant darkness followed by arhythmicity. Although the amplitude of clock gene (Per1, Cry1) expression was greatly attenuated in the SCN, the expression profile of arylalkylamine N-acetyltransferase, a rate-limiting melatonin synthesis enzyme, was unaffected in the pineal gland, and robust photoperiodic responses of the Tshb, Dio2, and Dio3 genes were observed. These results suggested that the Per2 clock gene is not necessary for the photoperiodic response in mice.

DOI： 10.1371/journal.pone.0058482

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PubMed

Language：Japanese   Publisher：(公社)日本畜産学会  

Language：Japanese   Publisher：(公社)日本畜産学会  

DOI： 10.1016/j.mce.2011.06.040

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Publisher：Seikagaku  

Scopus

Language：Japanese  

DOI： 10.3951/sobim.35.251

CiNii Books

DOI： 10.1210/en.2011-0237

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Language：Japanese   Publisher：(公社)日本繁殖生物学会  

Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.neures.2011.07.740

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Publisher：Animal Science Journal  

The avian perivitelline layer, an extracellular matrix homologous to the zona pellucida (ZP) of mammalian oocytes, is composed mainly by zona pellucida gene family glycoproteins. Our previous studies in Japanese quail have demonstrated that the matrix's components, ZP3 and ZPD, are synthesized in ovarian granulosa cells. Another component, ZP1, is synthesized in the liver. Recently, we demonstrated that another minor constituent, ZP2 is produced in the oocytes of the immature follicles. In the present study, we report the isolation of complementary DNA encoding quail ZP4 and its expression and origin in the female birds. By ribonuclease protection assay and in situ hybridization, we demonstrated that ZP4 transcripts were transcribed in the oocytes of small white follicles. The expression level of ZP4 decreased dramatically during follicular development, and the highest expression was observed in the small white follicles. Western blot analysis using the specific antibody against ZP4 indicated that the immunoreactive 58.2kDa protein was present in the lysates of the small white follicles. These results demonstrate for the first time that the avian ZP4 is expressed in the oocyte, and that the expression pattern of the gene is similar to that of ZP2. © 2011 The Authors. Journal compilation © 2011 Japanese Society of Animal Science.

DOI： 10.1111/j.1740-0929.2010.00830.x

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Authorship：Last author,　Corresponding author  

Language：English   Publisher：SPRINGER  

Our current understanding of the mechanism underlying seasonal reproduction in birds is reviewed.

DOI： 10.1007/s00441-010-1073-6

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DOI： 10.1073/pnas.1006393107

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

CS mice exhibit several distinct phenotypes of circadian behavioral rhythms and sleep properties. Because many mental illnesses are associated with abnormalities in the circadian rhythms and sleep pattern, we characterized the behavioral phenotypes in CS mice with a battery of behavioral tests. Among these phenotypes, we found that CS mice exhibit an extremely low immobility time in both the tail suspension test (TST) and forced swimming test (FST). To uncover the genetic basis for lower immobility time, we first performed quantitative trait locus (QTL) mapping using CS and C57BL/6J mice, which revealed significant QTLs on chromosomes (Chrs) 4 (FST) and 5 (TST and FST). To identify the quantitative trait gene on Chr 5, we narrowed the QTL interval to 0.5 Mb using several congenic and subcongenic strains. Ubiquitin-specific peptidase 46 (Usp46) with a lysine codon deletion was located in this region. This deletion affected nest-building, muscimol-induced righting reflex, and anti-immobility effects of imipramine. The muscimol-induced current in the hippocampal CA1 pyramidal neurons and hippocampal expression of the 67-kDa isoform of glutamic acid decarboxylase significantly decreased in Usp46 mutant mice. All these phenotypes were rescued in transgenic mice with bacterial artificial chromosomes containing wild-type Usp46. Thus, Usp46 affects the immobility in the TST and FST, and it is implicated in the regulation of GABA action.

DOI： 10.1111/j.1479-8425.2010.00435.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Circadian rhythms in physiology and behavior are known to be influenced by the estrous cycle in female rodents. The clock genes responsible for the generation of circadian oscillations are widely expressed both within the central nervous system and peripheral tissues, including those that comprise the reproductive system. To address whether the estrous cycle affects rhythms of clock gene expression in peripheral tissues, we first examined rhythms of clock gene expression (Per1, Per2, Bmal1) in reproductive (uterus, ovary) and non-reproductive (liver) tissues of cycling rats using quantitative real-time PCR (in vivo) and luminescent recording methods to measure circadian rhythms of PER2 expression in tissue explant cultures from cycling PER2:: LUCIFERASE (PER2::LUC) knockin mice (ex vivo). We found significant estrous variations of clock gene expression in all three tissues in vivo, and in the uterus ex Vivo. We also found that exogenous application of estrogen and progesterone altered rhythms of PER2::LUC expression in the uterus. In addition, we measured the effects of ovarian steroids on clock gene expression in a human breast cancer cell line (MCF-7 cells) as a model for endocrine cells that contain both the steroid hormone receptors and clock genes, We found that progesterone, but not estrogen, acutely up-regulated Per1, Per2, and Binal1 expression in MCF-7 cells. Together, our findings demonstrate that the timing of the circadian clock in reproductive tissues is influenced by the estrous cycle and suggest that fluctuating steroid hormone levels may be responsible, in part, through direct effects on the timing of clock gene expression, (C) 2010 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.steroids.2010.01.007

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PubMed

Publisher：Reproduction  

The avian perivitelline layer (PL), a vestment homologous to the zona pellucida (ZP) of mammalian oocytes, is composed of at least three glycoproteins. Our previous studies have demonstrated that the matrix's components, ZP3 and ZPD, are synthesized in ovarian granulosa cells. Another component, ZP1, is synthesized in the liver and is transported to the ovary by blood circulation. In this study, we report the isolation of cDNA encoding quail ZP2 and its expression in the female bird. By RNase protection assay and in situ hybridization, we demonstrate that ZP2 transcripts are restricted to the oocytes of small white follicles (SWF). The expression level of ZP2 decreased dramatically during follicular development, and the highest expression was observed in the SWF.Western blot and immunohistochemical analyses using the specific antibody against ZP2 indicate that the 80 kDa protein is the authentic ZP2, and the immunoreactive ZP2 protein is also present in the oocytes. Moreover, ultrastructural analysis demonstrated that the immunoreactive ZP2 localizes to the zona radiata, the perivitelline space, and the oocyte cytoplasm in the SWF. By means of western blot analysis and immunofluorescence microscopy, we detected a possible interaction of the recombinant ZP2 with ZP3 and that this interaction might lead to the formation of amorphous structure on the cell surface. These results demonstrate for the first time that the avian ZP gene is expressed in the oocyte, and that the ZP2 protein in the oocyte might play a role for the PL formation in the immature follicles of the ovary. © 2010 Society for Reproduction and Fertility.

DOI： 10.1530/REP-09-0222

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Publisher：Journal of Neuroendocrinology  

Seasonal reproduction depends on photoperiod-regulated activation or suppression of the gonadal axis. Recent studies in quail have identified long-day induced . TSH-β expression in the pars tuberalis (PT) as a rapid trigger of gonadal activation. Thyroid-stimulating hormone (TSH) induces type 2 deiodinase (. Dio2) in the ependymal cell layer (EC) of the infundibular recess to stimulate the gonadal axis. A similar mechanism is proposed in sheep and mice, but the experimental data on the temporal patterns of induction and suppression of . TSH-β and . Dio2 expression are incomplete. In the present study, we examined the expression of . TSH-β and . Dio2 in hamsters transferred from short- to long-day conditions for 9 days, and demonstrate the induction of . TSH-β and . Dio2 on day 8 after transition. These data demonstrate the close relationship between . TSH-β and . Dio2 expression in the inductive pathway. The temporal expression of . TSH-β and . Dio2 in the suppressive pathway was also examined by s.c. melatonin injection, which mimics the transition from long to short days. Importantly, . Dio2 expression in the EC is suppressed on day 1 after the onset of injection, whereas . TSH-β expression in the PT was not suppressed until day 10. These data suggest that regulated transcription of . TSH-β is involved in the induction of the gonadal axis in mammals, whereas the suppression of this axis is mediated by different mechanisms. © 2009 The Authors. Journal Compilation © 2009 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2826.2009.01936.x

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Authorship：Lead author   Language：English  

Authorship：Lead author   Language：Japanese  

Authorship：Lead author   Language：English  

Authorship：Lead author   Language：Japanese  

Authorship：Lead author   Language：Japanese  

Language：English   Publisher：JAPANESE PHARMACOLOGICAL SOC  

Web of Science

Language：English   Publisher：WILEY-BLACKWELL  

In temperate zones, animals use changes in day length as a calendar to time their breeding season. However, the photoreceptive and neuroendocrine mechanisms of seasonal reproduction are considered to differ markedly between birds and mammals. This can be understood from the fact that the eye is the only photoreceptive organ, and melatonin mediates the photoperiodic information in mammals, whereas in birds, photoperiodic information is directly received by the deep brain photoreceptors and melatonin is not involved in seasonal reproduction. Recent molecular and functional genomics analysis uncovered the gene cascade regulating seasonal reproduction in birds and mammals. Long day-induced thyroid stimulating hormone in the pars tuberalis of the pituitary gland regulates thyroid hormone catabolism within the mediobasal hypothalamus. Further, this local thyroid hormone catabolism appears to regulate seasonal gonadotropin-releasing hormone secretion. These findings suggest that although the light input pathway is different between birds and mammals (i.e. light or melatonin), the core mechanisms are conserved in these vertebrates.

DOI： 10.1111/j.1740-0929.2010.00777.x

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Language：English   Publishing type：Research paper (scientific journal)  

The circadian clock is a fundamental property of living organisms and is involved in seasonal (photoperiodic) time measurement. Among vertebrates, birds have multiple circadian pacemakers in the eye, the pineal gland, and the suprachiasmatic nucleus (SCN), and have highly sophisticated photoperiodic mechanisms. However, because the removal of these circadian pacemakers fails to abolish the photoperiodic response, the existence of another "photoperiodic clock" has been suggested. Recent studies have revealed that the mediobasal hypothalamus (MBH) and the adjacent pars tuberalis (PT) of the pituitary gland constitute key components of the photoperiodic signal transduction machinery. In the present study, we generated a polyclonal antibody against the chicken circadian clock protein BMAL1 to examine BMAL1 distribution in the Japanese quail brain by using immunohistochemistry. BMAL1-like immunoreactivity (lir) was confirmed in the pineal gland and the medial SCN, which are critical circadian pacemakers. We also observed strong immunoreactivity in the MBH, including the ependymal cells (ECs), the infundibular nucleus (IN), the median eminence (ME), and the adjacent PT. Furthermore, semiquantitative analysis suggested that BMAL1-lir shows daily fluctuation in these regions. It is possible that circadian clocks in the photoperiodic signal transduction machinery such as the PT and the EC may be involved in the regulation of photoperiodism.

DOI： 10.1002/cne.22165

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PubMed

Publisher：Integrative and Comparative Biology  

In temperate zones, the reproductive physiology of most vertebrates is controlled by changes in photoperiod. Mechanisms for the regulation of photoperiodic gonadal responses are known to differ between mammals and birds: in mammals, melatonin is the photoperiodic signal messenger, whereas in birds, photoperiodic information is received by deep brain photoreceptors. Recently, the molecular mechanism of photoperiodism has been revealed by studies on Japanese quail, which exhibit a most remarkable responsiveness to photoperiod among vertebrates, and molecular cascades involved in photoperiodism have been elucidated. Long-day stimulus induces expression of the β-subunit of thyroid stimulating hormone (TSH-β) in the pars tuberalis (PT) of the pituitary gland, and TSH derived from the PT regulates reciprocal switching of genes encoding types 2 and 3 deiodinases (Dio2 and Dio3, respectively) in the mediobasal hypothalamus (MBH) by retrograde action. Dio2 locally converts prohormone thyroxine (T4) to bioactive triiodothyronine (T3) in the MBH, which subsequently stimulates the gonadal axis. These events have been confirmed to occur in mammals with seasonal breeding, such as hamsters and sheep, suggesting that similar mechanisms are involved among various vertebrates. In addition, nonphotoperiodic mice also appeared to possess the same molecular mechanisms at the hypothalamo-hypophysial level. It has been noted that melatonin regulates the above-mentioned key genes (Dio2, Dio3, and TSH-β) in mammals, while photoperiod directly regulates these genes in birds. Thus, the input pathway of photoperiod is different between mammals and birds (i.e., melatonin versus light); however, the essential mechanisms are conserved among these vertebrates.

DOI： 10.1093/icb/icp011

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DOI： 10.1038/ng.344

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Language：English  

DOI： 10.1111/j.1740-0929.2009.00628.x

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CiNii Books

DOI： 10.1523/JNEUROSCI.0145-09.2009

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Web of Science

Publisher：Reproduction  

The egg envelope surrounding avian oocytes exhibits a three-dimensional network of coarse fibers between the granulosa cells and the oocyte. Our previous studies have demonstrated that one of the matrix's components, ZP3, is synthesized in the ovarian granulosa cells. Another component, ZP1, which is critically involved in triggering the sperm acrosome reaction, is synthesized in the liver. We have previously isolated cDNAs encoding quail ZP3 and ZP1, and we now report the isolation of cDNA encoding quail ZPD. By RNase protection assay and in situ hybridization, we have demonstrated that ZPD transcripts are restricted to the granulosa cells of preovulatory follicles. The expression level of ZPD increased progressively during follicular development, and the highest expression was observed in the largest follicles. Western blot analyses using the specific antibody against ZPD indicate that the 40 kDa protein is the authentic ZPD, and the contents of ZPD protein also increased during follicular development. Moreover, we found that the addition of FSH to the culture media enhances the ZPD secretion in the cultured granulosa cells. Two-dimensional gel electrophoresis revealed the presence of several ZPD isoforms with different pI values ranging from 5.5 to 7. Immunohistochemical analyses indicate that the materials recognized with anti-quail ZPD antibody were accumulated in the egg envelope of large yellow follicles. These results demonstrate the presence of ZPD protein in the egg envelope, and that the amount of ZPD in the egg envelope as well as the mRNA in the cells increases at the latter stages of folliculogenesis. © 2009 Society for Reproduction and Fertility.

DOI： 10.1530/REP-08-0057

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus). This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD) cycles to constant darkness (DD). To map the genes responsible for the persistence of rhythmicity (circadian ratio) and the length of free-running period (tau), quantitative trait locus (QTL) analysis was performed using F-2 mice obtained from an F-1 cross between the circadian variant and C57BL/6J mice. As a result, a significant QTL with a main effect for circadian ratio (Arrhythmicity; Arrh-1) was mapped on Chromosome (Chr) 8. For tau, four significant QTLs, Short free-running period (Sfp-1) (Chr 1), Sfp-2 (Chr 6), Sfp-3 (Chr 8), Sfp-4 (Chr 11) were determined. An epistatic interaction was detected between Chr 3 (Arrh-2) and Chr 5 (Arrh-3). An in situ hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc) real-time monitoring analysis in the suprachiasmatic nucleus (SCN) suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may provide a novel opportunity to evaluate circadian and its related disorders in human that arise from the interaction between multiple variant genes.

DOI： 10.1371/journal.pone.0004301

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Authorship：Lead author   Language：English  

DOI： 10.1016/j.neures.2009.09.1615

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DOI： 10.1016/j.neures.2009.09.1301

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DOI： 10.1016/j.neures.2009.09.1302

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Language：English   Publisher：GENETICS SOC JAPAN  

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Language：English   Publisher：GENETICS SOC JAPAN  

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DOI： 10.1073/pnas.0808952105

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DOI： 10.1530/REP-08-0041

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

To better understand alterations in suprachiasmatic nucleus (SCN) physiology by photic and non-photic environments, we analyzed clock gene expression in the mouse SCN by in situ hybridization and real-time monitoring of mPerl::luc bioluminescence. An artificial light : dark : light : dark 7:5:7:S condition induced antiphase oscillation of the clock gene in the dorsomedial-like (DM-like) and the ventrolateral-like (VL-like) subdivisions of the SCN, in parallel with maintaining synchronization between the two sides of the SCN. This antiphase oscillation seems to be responsible for the bimodal rhythms of mPer1 bioluminescence observed in the entire SCN and the components of splitting locomotor activity. A long photoperiod (LP) induced the phase advance of the rhythms of clock gene expression in the caudal SCN relative to those in the rostral SCN. In addition, in the middle SCN, the rhythms of the VL-like subdivision phase-led those in the DM-like subdivision. The mPer1::luc rhythms in the entire coronal slice obtained from the middle SCN exhibited two peaks with a wide peak width under LP conditions. Imaging analysis of the mPerl::luc rhythms revealed wide regional variations in the peak time in the rostral half of the SCN. These variations were not due to alterations in the waveform of a single SCN neuronal rhythm. In CS mice which easily entrain to daily restricted feeding (RF) cycles, the peak width for mPer1::luc bioluminescence rhythms in the SCN markedly increased during the RF schedule under LID conditions. These data in CS mice suggest non-photic cues alter SCN organization and provided a new method to reveal subdivisional changes of the SCN by feeding cues.

DOI： 10.1111/j.1479-8425.2008.00345.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SAGE PUBLICATIONS INC  

In mammals, the suprachiasmatic nucleus (SCN), the circadian pacemaker, receives light information via the retina and functions in the entrainment of circadian rhythms and in phasing the seasonal responses of behavioral and physiological functions. To better understand photoperiod-related alterations in the SCN physiology, we analyzed the clock gene expression in the mouse SCN by performing in situ hybridization and real-time monitoring of the mPer1::luc bioluminescence. Under long photoperiod ( LP) conditions, the expression rhythms of mPer1 and Bma11 in the caudal SCN phase-led those in the rostral SCN; further, within the middle SCN, the rhythms in the ventrolateral (VL)-like subdivision advanced compared with those in the dorsomedial (DM)-like subdivision. The mPer1::luc rhythms in the entire coronal slice obtained from the middle SCN exhibited 2 peaks with a wide peak width under LP conditions. Imaging analysis of the mPer1::luc rhythms in several subdivisions of the rostral, middle, caudal, and horizontal SCN revealed wide regional variations in the peak time in the rostral half of the SCN under LP conditions. These variations were not due to alterations in the waveform of a single SCN neuronal rhythm. Our results indicate that LP conditions induce phase changes in the rhythms in multiple regions in the rostral half of the SCN; this leads to different circadian waveforms in the entire SCN, coding for day length.

DOI： 10.1177/0748730408314572

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DOI： 10.1038/nature06738

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Authorship：Lead author   Language：Japanese  

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Authorship：Lead author   Language：Japanese  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：ELSEVIER IRELAND LTD  

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Language：English   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.cbpb.2007.07.020

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DOI： 10.1210/en.2007-0497

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DOI： 10.1016/j.brainres.2007.06.028

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DOI： 10.1210/en.2007-0044

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DOI： 10.2108/zsj.24.686

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PubMed

DOI： 10.1210/en.2007-0112

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DOI： 10.1177/0748730406295435

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PubMed

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：Japanese  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：SPRINGER  

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Language：English   Publisher：ELSEVIER SCIENCE INC  

Appropriate timing of various seasonal processes is crucial to the survival and reproductive success of animals living in temperate regions. When seasonally breeding animals are subjected to annual changes in day length, dramatic changes in neuroendocrine-gonadal activity take place. However, the molecular mechanism underlying the photoperiodic response of gonads remains unknown for all living organisms. It is well known that a circadian clock is somehow involved in the regulation of photoperiodism. Recently, rhythmic expression of circadian clock genes was observed in the mediobasal hypothalamus (MBH) of Japanese quail. The MBH is believed to be the center for photoperiodism. In addition, long-day-induced hormone conversion of the prohormone thyroxine (T-4) to the bioactive triiodothyronine (T-3) by deiodinase in the MBH has been proven to be important to the photoperiodic response of the gonads. Although the regulating mechanism for the photoperiodic response of gonads in birds and mammals has long been considered to be quite different, the long-day-induced expression of the deiodinase gene in the hamster hypothalamus suggests the existence of a conserved regulatory mechanism in avian and mammalian photoperiodism. (c) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cbpa.2005.09.009

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Publisher：Cell and Tissue Research  

Photoperiodically generated triiodothyronin (T3) in the mediobasal hypothalamus (MBH) has critical roles in the photoperiodic response of the gonads in Japanese quail. In a previous study, we demonstrated seasonal morphological changes in the neuro-glial interaction between gonadotrophin-releasing hormone (GnRH) nerve terminals and glial endfeet in the median eminence (ME). However, a direct relationship between photoperiodically generated T3 and seasonal neuro-glial plasticity in the ME remained unclear. In the present study, we examined the effect of T3 implantation into the MBH on the neuro-glial interaction in the ME. T 3 implantation caused testicular growth and reduced encasement of nerve terminals in the external zone of the ME. In contrast, no morphological changes were observed in birds given an excessive dose of T3, which did not cause testicular growth. These results support the hypothesis that thyroid hormone regulates photoperiodic GnRH secretion via neuro-glial plasticity in the ME. © Springer-Verlag 2006.

DOI： 10.1007/s00441-005-0126-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：4  

DOI： 10.1016/j.neures.2005.12.009

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CiNii Books

DOI： 10.1210/en.2005-1090

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DOI： 10.1210/en.2005-0507

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Authorship：Lead author   Language：English  

Publisher：Chronobiology International  

In most organisms living in temperate zones, reproduction is under photoperiodic control. Although photoperiodic time measurement has been studied in organisms ranging from plants to vertebrates, the underlying molecular mechanism is not well understood. The Japanese quail (Coturnix japonica) represents an excellent model to study this problem because of the rapid and dramatic photoperiodic response of its hypothalamic-pituitary-gonadal axis. Recent investigations of Japanese quail show that long-day-induced type 2 deiodinase (Dio2) expression in the mediobasal hypothalamus (MBH) plays an important role in the photoperiodic gonadal regulation by catalyzing the conversion of the prohormone thyroxine (T4) to bioactive 3,5,3′-triiodothyronine (T3). The T3 content in the MBH is approximately 10-fold higher under long than short days and conditions, and the intracerebroventricular infusion of T3 under short days and conditions mimics the photoperiodic gonadal response. While Dio2 generates active T3 from T4 by outer ring deiodination, type 3 deiodinase (Dio3) catalyzes the conversion of both T3 and T 4 into inactive forms by inner ring deiodination. In contrast to Dio2 expression, Dio3 expression in the MBH is suppressed under the long-day condition. Photoperiodic changes in the expression of both genes during the photoinduction process occur before the changes in the level of luteinizing hormone (LH) secretion, suggesting that the reciprocal changes in Dio2 and Dio3 expression act as gene switches of the photoperiodic molecular cascade to trigger induction of LH secretion. Copyright © Taylor & Francis Group, LLC.

DOI： 10.1080/07420520500521913

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Publisher：Development Genes and Evolution  

Honeybees have been shown to exhibit cognitive performances that were thought to be specific to some vertebrates. However, the molecular and cellular mechanisms of such cognitive abilities of the bees have not been understood. We have identified a novel gene, Mahya, expressed in the brain of the honeybee, Apis mellifera, and other Hymenoptera. Mahya orthologues are present in Deuterostomes but are absent or highly diverged in nematodes and, intriguingly, in two dipteran insects (fruit fly and mosquito) and Lepidoptera (silk moth). Mahya genes encode novel secretory proteins with a follistatin-like domain (Kazal-type serine/ threonine protease inhibitor domain and EF-hand calcium-binding domain), two immunoglobulin domains, and a C-terminal novel domain. Honeybee Mahya is expressed in the mushroom bodies and antennal lobes of the brain. Zebra fish Mahya orthologues are expressed in the olfactory bulb, telencephalon, habenula, optic tectum, and cerebellum of the brain. Mouse Mahya orthologues are expressed in the olfactory bulb, hippocampus, and cerebellum of the brain. These results suggest that Mahya may be involved in learning and memory and in processing of sensory information in Hymenoptera and vertebrates. Furthermore, the limited existence of Mahya in the genomes of Hymenoptera and Deuterostomes supports the hypothesis that the genes typically represented by Mahya were lost or highly diverged during the evolution of the central nervous system of specific Bilaterian branches under the specific selection and subsequent adaptation associated with different ecologies and life histories. © Springer-Verlag 2005.

DOI： 10.1007/s00427-005-0021-z

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DOI： 10.1210/en.2005-0057

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Authorship：Lead author   Language：Japanese  

Language：Japanese  

Authorship：Lead author   Language：Japanese  

Language：Japanese  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Publisher：Endocrinology  

In a previous study we showed that photoperiodically generated T 3 in the hypothalamus is critical for the photoperiodic response of gonads in Japanese quail. The expression of thyroid hormone receptors in the median eminence (ME) suggested that photoperiodically generated T3 acts on the ME. Because thyroid hormone is known to play a critical role in the development and plasticity of the central nervous system, in the present study we have examined ultrastructure of the ME in Japanese quail kept in short-day and long-day environments. Immunoelectron microscopy revealed that GnRH nerve terminals are in close proximity to the basal lamina under long-day conditions, and conventional transmission electron microscopy demonstrated the encasement of the terminals by the endfeet of glia under short-day conditions. These morphological changes may regulate photoperiodic GnRH secretion.

DOI： 10.1210/en.2004-0366

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Publisher：Brain Research  

The physiological activity of avian optic tectum (TeO) is known to be regulated by the circadian system. In a previous study, we found clock gene expression in the TeO of Japanese quail. Here we report rhythmic expression of the Per2 gene in the stratum griseum et fibrosum (SGF) of the TeO under a light-dark (LD) cycle, constant darkness (DD), and constant light (LL) conditions. However, light pulse did not affect Per2 expression in the TeO. These results suggest that light stimulus and melatonin rhythm are not essential for rhythmic expression of Per2 in the avian TeO in spite of the localization of melatonin receptors and retinal input. © 2004 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2004.01.031

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Language：English   Publisher：ELSEVIER SCI IRELAND LTD  

L-Glutamate is a major neurotransmitter at the excitatory synapses in the vertebrate brain. It is also the excitatory neurotransmitter at neuromuscular junctions in insects, however its functions in their brains remain to be established. We identified and characterized two different subtypes (AmGluRA and AmGluRB) of metabotropic glutamate receptors (mGluRs) from an eusocial insect, honeybee. Both AmGluRA and AmGluRB form homodimers independently on disulfide bonds, and bind [H-3]glutamate with K-D values of 156.7 and 80.7 nM, respectively. AmGluRB is specifically expressed in the brain, while AmGluRA is expressed in the brain and other body parts, suggesting that AmGluRA is also present at the neuromuscular junctions. Both mGluRs are expressed in the mushroom bodies and the brain regions of honeybees, where motor neurons are clustered. Their expression in the brain apparently overlaps, suggesting that they may interact with each other to modulate the glutamatergic neurotransmission. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.neulet.2004.02.004

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DOI： 10.1210/en.2003-1593

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DOI： 10.1210/en.2003-1285

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Authorship：Lead author   Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese  

Authorship：Lead author   Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

Language：Japanese   Publishing type：Research paper (scientific journal)  

Publisher：Brain Research  

In our previous study, quantitative trait locus (QTL) analysis using mice with abnormal circadian rhythm detected a suggestive QTL, which affects the length of free-running period, on the distal region of Chromosome 19. Among the candidate genes, we have focused on Ikkα gene and found that Ikkα mRNA is expressed in the mammalian circadian pacemaker, the suprachiasmatic nucleus (SCN) in the present study. Expression of Ikkα mRNA in the SCN indicated the possibility that IKKα is involved in the regulation of circadian clock. Therefore, to examine the role of IKKα in the regulation of circadian rhythms, we have further examined wheel-running activity rhythms under light-dark cycle and constant darkness, and circadian response to light. However, we could not detect any statistically significant difference between IKKα+/- mice and wild type mice. Roles of IKKα in the regulation of circadian system remains to be clarified in the future study. © 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.brainres.2003.09.007

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Publisher：Brain Research  

Avian circadian rhythms are regulated by a multiple oscillatory system consisting of the pineal, the suprachiasmatic nucleus (SCN) and the eye. In the present study, ontogeny of circadian clock in the pineal and the SCN of chick embryo was examined using Per2 expression as a marker. A daily rhythmicity of Per2 expression was first detectable at embryonic day (ED) 18 in the pineal and at ED 16 in the SCN under light-dark (LD) cycles. The amplitude of the rhythmicity increased during the development. In contrast, little expression was observed during the development in constant darkness. These results suggest that although circadian clock matures by the end of the embryonic life in chicken, LD cycles are required for the expression of the Per2. © 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/S0006-8993(03)03531-5

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Language：English   Publisher：NATURE PUBLISHING GROUP  

Reproduction of many temperate zone birds is under photoperiodic control. The Japanese quail is an excellent model for studying the mechanism of photoperiodic time measurement because of its distinct and marked response to changing photoperiods. Studies on this animal have suggested that the mediobasal hypothalamus (MBH) is an important centre controlling photoperiodic time measurement(1-8). Here we report that expression in the MBH of the gene encoding type 2 iodothyronine deiodinase (Dio2), which catalyses the intracellular deiodination of thyroxine (T-4) prohormone to the active 3,5,3'-triiodothyronine (T-3), is induced by light in Japanese quail. Intracerebroventricular administration of T-3 mimics the photoperiodic response, whereas the Dio2 inhibitor iopanoic acid prevents gonadal growth. These findings demonstrate that light-induced Dio2 expression in the MBH may be involved in the photoperiodic response of gonads in Japanese quail.

DOI： 10.1038/nature02117

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Publisher：Endocrinology  

In birds, the mediobasal hypothalamus (MBH) including the infundibular nucleus, inferior hypothalamic nucleus, and median eminence is considered to be an important center that controls the photoperiodic time measurement. Here we show expression patterns of circadian clock genes in the MBH, putative suprachiasmatic nucleus (SCN), and pineal gland, which constitute the circadian pacemaker under various light schedules. Although expression patterns of clock genes were different between long and short photoperiod in the SCN and pineal gland, the results were not consistent with those under night interruption schedule, which causes testicular growth. These results indicate that different expression patterns of the circadian clock genes in the SCN and pineal gland are not an absolute requirement for encoding and decoding of seasonal information. In contrast, expression patterns of clock genes in the MBH were stable under various light conditions, which enables animals to keep a steady-state photoinducible phase.

DOI： 10.1210/en.2003-0435

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Publisher：Brain Research  

In mice, genetic differences between inbred strains have been shown for several parameters of sleep and circadian activity rhythms. Our previous studies have demonstrated that CS mice have three remarkable characteristics in the circadian rhythm of locomotor activity: (1) high activity both during the day and night, (2) unstable freerunning period and (3) spontaneous rhythm splitting. In order to characterize sleep properties of CS mice, we compared circadian sleep patterns of CS with those of C57BL/6J and C3H/He mice which have normal circadian activity rhythms. Although C57BL/6J and C3H/He mice exhibited clear daily sleep-wake rhythms in the amount of each sleep parameter (Awake, SWS, PS), CS mice did not show clear rhythms in these parameters. The differences were particularly conspicuous in PS; no apparent day-night differences in the amount of PS, PS counts and PS interval (the interval between successive PS episodes) in CS mice. In addition, the ratio of PS to total sleep time was significantly larger in CS mice than other strains. Of these parameters, the most considerable was PS latency which was extremely short and direct transition from Awake to PS without appearance of SWS frequently occurred in these mice. These results indicate that CS mice may be useful for the understanding of sleep mechanisms and its dysfunction. © 2003 Elsevier B.V. All rights reserved.

DOI： 10.1016/S0006-8993(03)02947-0

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Publisher：Neuroscience Letters  

CS mice exhibit rhythm splitting in constant darkness (DD). To examine the anatomical and physiological bases of this phenomenon, mouse Period1 (mPer1)-driven green fluorescent protein (GFP) mice with rhythm splitting were produced by crossing CS and mPer1::GFP mice. GFP expression in the suprachiasmatic nucleus (SCN) slices showed a clear unimodal rhythm with the highest level at circadian time (CT) 8 or CT12 in splitting and non-splitting GFP mice under DD and no essential differences in the pattern of GFP expression were found between these mice. Moreover, there were no significant differences in the degree of symmetry in the paired rostral, central and caudal SCN between splitting and non-splitting mice. These results indicate that behavioral rhythm splitting in CS mice does not reflect the pattern of clock gene expression in the SCN. © 2003 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S0304-3940(03)00484-1

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1177/0748730402238233

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DOI： 10.1046/j.1460-9568.2002.02222.x

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Language：Japanese  

Language：Japanese  

Language：Japanese  

Publisher：Mammalian Genome  

CS mice show a free-running period (τ) longer than 24 h and rhythm splitting in constant darkness (DD). These features in behavioral circadian rhythms are distinctive as compared with other inbred strains of mice, which exhibit robust free-running rhythms with τ shorter than 24 h. To identify the genes affecting τ, quantitative trait locus (QTL) analysis was initially conducted by using 289 F2 mice derived from a cross between CS and C57BL/6J strain. A suggestive QTL (LOD = 3.71) with CS allele increasing τ was detected on the distal region of Chromosome (Chr) 19. Next, using 192 F2 mice from a cross between CS and MSM strain, the presence of the QTL on Chr 19 was examined, and we confirmed the QTL at the genome-wide significant level (LOD = 4.61 with 10.4% of the total variance explained). This QTL was named long free-running period (Lfp). Three other suggestive QTLs (LOD = 3.24-4.28) were mapped to the midportion of Chr 12 in (CS×C57BL/6J)F2 mice, and to the proximal and middle region of Chr 19 in (CS×MSM)F2 mice, respectively, of which, CS alleles for two QTLs on Chr 19 have the effect of lengthening τ. None of these QTLs were mapped to the chromosomal regions of previously described QTLs for τ and known clock genes (Clock, mPer1, Bma11, mCry1, mCry2, mTim, and Csnkle).

DOI： 10.1007/s003350010280

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DOI： 10.1152/ajpregu.2001.280.4.R1185

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Language：English  

SM/J and A/J inbred strain of mice have different characteristics in circadian behaviors such as free-running period (τ), phase relationship (ψ) between light-dark cycles and activity rhythms, and amount of wheel-running activity. To determine the genes which affect these behaviors, a quantitative trait locus (QTL) analysis using SMXA recombinant inbred strains derived from SM/J and A/J mice was performed. Concerning τ, two regions on chromosomes (Chrs) 7 and 18 surpassed the genome-wide suggestive level. As for ψ, one suggestive QTL was detected on Chr 7. The QTLs which affect daily activity counts under light-dark cycles and constant darkness were mapped to the same chromosomal regions on Chrs 1 and 17, respectively. The provisional QTLs detected in the present study might be useful for understanding the complex mechanism regulating circadian behaviors.

DOI： 10.1023/A:1010298701251

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Language：English  

DOI： 10.1016/S0169-328X(00)00091-7

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Language：Japanese  

Language：Japanese  

DOI： 10.1016/S0006-8993(97)01122-0

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Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

Pineal melatonin is produced during the night. Its nocturnal increase regulates circadian rhythms and the photo-periodic reproductive response. Serotonin is acetylated to N-acetylserotonin by serotonin N-acetyltransferase (SNAT) and then methylated to form melatonin by hydroxyindole-O-methyltransferase (HIOMT). The rhythmicity of melatonm synthesis is regulated by the rhythmic activity of SNAT. Most laboratory mice do not have melatonin because of a genetic defect in the activity of SNAT and/or HIOMT. In a previous study using a recombinant inbred strain, we have found that the locus controlling pineal SNAT activity (Nat4) is located on mouse Chromosome 11. Recently, SNAT has been cloned in the rat. In the present study, the gene encoding SNAT was localized, using a rat cDNA fragment, on rat and mouse chromosomes by direct R-banding fluorescence in situ hybridization (FISH). In addition, using molecular linkage analysis with interspecific back-cross mice, a gene encoding SNAT was mapped on a mouse chromosome. The gene encoding SNAT was localized to rat chromosome 10q32.3 and mouse Chromosome 11E2 by FISH. The molecular linkage analysis demonstrated that the gene encoding SNAT maps 1.5 cM distal to DUMit11. The data suggest that Nat4 encodes SNAT. These chromosomal locations are in a region of conserved linkage homology between the two species. © 1997 S. Karger AG, Basel.

DOI： 10.1159/000134713

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Language：English   Publishing type：Research paper (scientific journal)  

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Many birds have highly sophisticated photoperiodic mechanisms and show robust responses to changing photoperiod. William Rowan is generally credited with the first demonstration of the avian photoperiodic response when he photostimulated dark eyed juncos (Junco hyemalis) during the Canadian winter and observed stimulation of testicular growth. The application of molecular biological techniques to understanding the mechanisms controlling the avian photoperiodic response continue Rowan's pioneering tradition of using birds to study vertebrate photoperiodism. This chapter focuses on current understanding of genetic and molecular mechanisms underlying the avian photoperiodic response.

DOI： 10.1093/acprof:oso/9780195335903.003.0018

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Avian circadian clock: toward the understanding of molecular mechanisms

Responsible for pages：259-265   Language：English

Avian circadian clock: toward the understanding of molecular mechanisms

Language：Japanese

生物時計の分子機構-遺伝学的研究

Responsible for pages：50-57   Language：Japanese

生物時計の分子機構-遺伝学的研究

Language：Japanese  

DOI： 10.11477/mf.2425200552

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Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

J-GLOBAL

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Animals measure photoperiod (daylength) and adapt to seasonal changes in the environment by altering their physiology and behavior accordingly. Although this photoperiodic response has long been of interest, the underlying mechanism has only recently begun to be uncovered at the molecular level. Japanese quail provide an excellent model to study the molecular mechanism underlying the vertebrate photoperiodic response. The recent sequencing of the chicken genome allowed a system-level analysis of photoperiodic time measurement in quail, and this approach uncovered the key event in the photoperiodic signaling cascade that regulates seasonal reproduction. Long photoperiod-induced expression of thyrotropin in the pars tuberalis of the pituitary gland was found to trigger local thyroid hormone catabolism in the mediobasal hypothalamus, which increases the activity of the reproductive neuroendocrine system resulting in gonadal development. Since thyrotropin was only known to stimulate the thyroid gland, a traditional hypothesi s-d riven approach would not have been expected to predict this discovery. Thus, a functional genomics approach, which is a discovery-driven approach, provides new insights in the field of endocrinology. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ygcen.2008.11.017

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

The molecular basis of seasonal or nonseasonal breeding remains unknown. Although laboratory rats are generally regarded as photoperiod-insensitive species, the testicular weight of the Fischer 344 (F344) strain responds to photoperiod. Recently, it was clarified that photoperiodic regulation of type 2 iodothyronine deiodinase (Dio2) in the mediobasal hypothalamus (MBH) is critical in photoperiodic gonadal regulation. Strain-dependent differences in photoperiod sensitivity may now provide the opportunity to address the regulatory mechanism of seasonality by studying Dio2 expression. Therefore, in the present study, we examined the effect of photoperiod on Dio2 expression in photoperiod-sensitive F344 and photoperiod-insensitive Wistar rats. A statistically significant difference was observed between short and long days in terms of testicular weight and Dio2 expression in the F344 strain, while no difference was observed in the Wistar strain. These results suggest that differential responses of the Dio2 gene to photoperiod may determine the strain-dependent differences in photoperiod sensitivity in laboratory rats.

DOI： 10.1152/ajpregu.00396.2006

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Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

Photorefractoriness is the insensitivity of gonadal development to the stimulatory effects of long photoperiods in birds and to the inhibitory effects of short photoperiods in small mammals. Its molecular mechanism remains unknown. Recently, it has been shown that reciprocal expression of thyroid hormone-activating enzyme [type 2 deiodinase (Dio2)] and-inactivating enzyme [type 3 deiodinase (Dio3)] genes in the mediobasal hypothalamus is critical for photoperiodically induced gonadal growth. Since thyroid hormones are required not only for photoinduction, but also for the induction of photorefractoriness, we examined the expression of these genes in relation to photorefractoriness in birds and mammals. Transfer of birds to long photoperiods induced strong expression of Dio2. This was maintained in tree sparrow when they later became photorefractory, but decreased somewhat in quail. In hamsters, transfer to long photoperiods also induced strong expression of Dio2. High values were not maintained under long photoperiods, and, indeed, expression decreased at the same rate as in animals transferred to short photoperiods. There was no renewed expression of Dio2 associated with testicular growth as animals became refractory to short photoperiods. Expression of Dio3 was high under short photoperiods and low under long photoperiods in all the animals examined, except for the short photoperiod-refractory hamsters. Our present study revealed complex regulation of deiodinase genes in the photoinduction and photorefractory processes in birds and mammals. These gene changes may be involved in the regulation of photorefractoriness, as well as photoinduction.

DOI： 10.1152/ajpregu.00521.2006

Web of Science

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

Most temperate-zone animals are seasonal breeders. In a previous study, it was found that light-induced hormone conversion of thyroxine (T4) prohormone to active 3,5,3′-triiodothyronine (T3) in the mediobasal hypothalamus regulates photoperiodic response of gonads in Japanese quail. Here the effect of T4 or T3, administered in drinking water, on testicular growth in the Japanese quail kept under short days is shown. Testicular length was significantly increased in birds given T 4 at doses of 4, 8 and 10 mg/L, while any dose of T3 had little effect on testicular growth. High doses (8 and 10 mg/L) of T4 and T3 resulted in high mortality and/or reduction of bodyweight. Among all of the treatment, 4 mg/L of T4 was the most effective on photoperiodic testicular growth, which caused little reduction in bodyweight. These data provide a new conventional method for promoting gonadal growth under short days.

DOI： 10.1111/j.1740-0929.2004.00205.x

Scopus

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Appropriate timing of various seasonal processes is crucial to the survival and reproductive success of animals inhabiting temperate regions. When seasonally breeding animals are subjected to annual changes in daylength, dramatic changes in neuroendocrine-gonadal activity ensue. However, the molecular mechanism of photoperiodic (or seasonal) time measurement (PTM) is not well understood for any organism living. Japanese quail is an excellent model for studying PTM because of the rapid and dramatic response to photoperiod. Here I describe recent progress in understanding the molecular mechanism of PTM in Japanese quail. © 2004, Japan Poultry Science Association. All rights reserved.

DOI： 10.2141/jpsa.41.251

Scopus

Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese  

CiNii Books

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

Pineal and retinal melatonin has an important role in the control of avian circadian rhythms. In order to study the mechanisms of circadian rhythms of melatonin synthesis in the pineal and in the eye, in vivo microdialysis was applied to these organs. In both pigeons and Japanese quails, pineal and ocular melatonin levels were high during the dark and low during the day under light-dark (LD) cycles. These rhythms persisted under constant dim light (LLdim) conditions indicating the circadian nature of pineal and ocular melatonin release. Light has two effects on melatonin synthesis. One is acute inhibition of melatonin synthesis and the other is entrainment of circadian melatonin rhythms. We have examined photoreceptors mediating these effects in the pigeon. The results have indicated that the eyes are not involved in light-induced suppression and photic entrainment of pineal melatonin release, and pineal photoreceptors themselves are likely to mediate these effects. Concerning ocular melatonin, retinal photoreceptors seem to mediate light-induced suppression and photic entrainment and no evidence supporting mediation of extraretinal photoreceptors was obtained. Because dopamine is implicated in retinal melatonin synthesis, we measured dopamine and melatonin release simultaneously from the eye of pigeon. In contrast to melatonin rhythms, dopamine increased during the day and decreased during the dark. This antiphase relationship between melatonin and dopamine persisted in LLdim, suggesting an interaction between these two rhythms. The results of an intraocular injection of dopamine or melatonin in the phase of melatonin and dopamine rhythms indicated that the interaction is required for maintaining the antiphase relationship between the two rhythms. © 1997 S. Karger AG, Basel.

DOI： 10.1159/000109133

Scopus

PubMed

Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)  

Language：English   Publishing type：Rapid communication, short report, research note, etc. (scientific journal)   Publisher：Springer Verlag  

Light-dark cycles are the most important time cue for the circadian system to entrain the endogenous circadian clock to the environmental 24 h cycle. Although photic entrainment of circadian rhythms is mediated by the eye in mammals, photoreceptors implicated in circadian photoreception remain unknown. In our previous study, retinally degenerate CBA/J (rd/rd) mice were found to have lower circadian photosensitivity for phase-shifting the locomotor activity rhythms than normal CBA/N( +/+ ) mice. In the present study, the spectral sensitivity for phase-shifting the rhythms was examined in order to characterize the photopigments involved in circadian photoreception of these mice. The spectral sensitivity of CBA/J-rd/rd mice clearly fitted to the Dartnall nomogram for a retinal1-based pigment with a maximum at 480 nm, while the best fitted nomogram had a maximum at 500 nm in CBA/N- +/+ mice. These results suggest that circadian photopigments involved in CBA/J-rd/rd and CBA/N- +/+ mice may be different.

DOI： 10.1007/BF00225828

Scopus

PubMed

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