Updated on 2022/05/23

写真a

 
KIYAMA Hiroshi
 
Organization
Graduate School of Medicine Program in Integrated Medicine Anatomy and Cell Biology Professor
Graduate School
Graduate School of Medicine
Undergraduate School
School of Medicine
Title
Professor
Contact information
メールアドレス

Degree 2

  1. Doctor of Medical Science ( 1991.2   Osaka University ) 

  2. 医科学修士 ( 1984.3   大阪大学 ) 

Research Areas 4

  1. Life Science / Anatomy  / Neuroanatomy,

  2. Life Science / Pathophysiologic neuroscience

  3. Life Science / Anatomy and histopathology of nervous system

  4. Life Science / Nutrition science and health science  / 慢性疲労、慢性ストレス

Current Research Project and SDGs 2

  1. nerve regeneration

  2. Fatigue Sciecne

Research History 8

  1. Nagoya University   Professor

    2011.4

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    Country:Japan

  2. Nagoya University   Professor

    2017.4 - 2023.3

  3. Nagoya University   Institute of Liberal Arts and Sciences, Headquarters   Professor

    2012.4 - 2015.3

  4. Osaka City University   Professor Emeritus

    2011.4

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    Country:Japan

  5. Osaka City University   Professor

    2001.1 - 2011.3

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    Country:Japan

  6. Asahikawa Medical College   Professor

    1997.2 - 2000.12

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    Country:Japan

  7. Osaka University   Assistant Professor

    1991.5 - 1997.2

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    Country:Japan

  8. Osaka University   Assistant

    1986.11 - 1991.5

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    Country:Japan

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Education 2

  1. Osaka University   Graduate School, Division of Medicine

    1984.4 - 1986.10

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    Country: Japan

  2. Osaka University   Graduate School, Division of Medicine

    1982.4 - 1984.3

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    Country: Japan

Professional Memberships 10

  1. Japan Society for Neurochemistry   President

    2013.3 - 2015.3

  2. JSN

    2017.3 - 2020.3

  3. 日本解剖学会   理事/常務理事

    2013.4 - 2022.3

  4. Japan Neuroscience Society

    2020.1

  5. 日本自律神経学会   理事

    2009.11

  6. 日本疲労学会   理事

    2017.5

  7. Japanese peripheral nerve societ

    2000.8

  8. 篤志解剖全国連合会   理事

    2020.3 - 2022.3

  9. International Society for Neurochemistry

    1990

  10. Society for Neuroscience

    1987.10

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Committee Memberships 6

  1. 第126回日本解剖学会総会学術集会(第98回生理学会との合同大会)   会頭  

    2021.3   

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    Committee type:Academic society

  2. 第22回グリア研究会 大会長   大会長  

    2017.12   

  3. 第13回日本疲労学会 大会長   大会長  

    2017.5   

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    Committee type:Academic society

  4. 第68回日本自律神経学会 大会長   大会長  

    2015.10   

  5. Neuro2013   Chair  

    2013.6   

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    Committee type:Academic society

  6. 第69回、70回 脳の医学・生物学研究会   代表幹事  

    2020 - 2022   

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Papers 71

  1. Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction Invited Reviewed

    Konishi H*, Okamoto T, Hara Y, Komine O, Tamada H, Maeda M, Osako F, Kobayashi M, Nishiyama A, Kataoka Y, Takai T, Udagawa N, Jung S, Ozato K, Tamura T, Tsuda M, Yamanaka K, Ogi T, Sato K, Kiyama H

    EMBO J     2020.10

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  2. Distinct functional consequences of ECEL1/DINE missense mutations in the pathogenesis of congenital contracture disorders Invited Reviewed

    Nagata K, Takahashi M, Kiryu-Seo S, Kiyama H, Saido TC

    Acta Neuropathol Commun   Vol. 5 ( 1 ) page: 83   2017.11

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

    DOI: 10.1186/s40478-017-0486-9

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  3. Agonists for G protein-coupled receptor 84 (GPR84) alter cellular morphology and motility but do not induce pro-inflammatory responses in microglia Invited Reviewed

    Wei L, Tokizane K, Konishi H, Yu HR, Kiyama H

    J Neuroinflammation   Vol. 14 ( 1 ) page: 198   2017.10

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

    DOI: 10.1186/s12974-017-0970-y

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  4. Siglec-H is a microglia-specific marker that discriminates microglia from CNS-associated macrophages and CNS-infiltrating monocytes Invited Reviewed

    Konishi H, Kobayashi M, Kunisawa T, Imai K, Sayo A, Malissen B, Crocker PR, Sato K, Kiyama H

    Glia   Vol. 65 ( 12 ) page: 1927 - 1943   2017.12

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

    DOI: 10.1002/glia.23204

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  5. Damage-induced neuronal endopeptidase (DINE) enhances axonal regeneration potential of retinal ganglion cells after optic nerve injury Reviewed

    Kaneko A, Kiryu-Seo S, Matsumoto S, Kiyama H

    Cell Death & Disease   Vol. 8 ( 6 ) page: e2847   2017

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

    DOI: 10.1038/ccdis.2017.212

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  6. Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM Reviewed

    Tamada H, Kiryu-Seo S, Hosokawa H, Ohta K, Ishihara N, Nomura M, Mihara K, Nakamura K-I, Kiyama H

    J Comp Neurol   Vol. 525 ( 11 ) page: 2535-2548   2017

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

  7. Phospholipid localization implies microglial morphology and function via Cdc42 in vitro Reviewed

    Tokizane K, Konishi H, Makide K, Kawana H, Nakamura S, Kaibuchi K, Ohwada T, Aoki J, Kiyama H

    Glia   Vol. 65 ( 5 ) page: 740-755   2017

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

  8. Exposure to diphtheria toxin during the juvenile period impairs both inner and outer hair cells in C57BL/6 mice Reviewed

    Konishi H, Ohgami N, Matsushita A, Kondo Y, Aoyama Y, Kobayashi M, Nagai T, Ugawa S, Yamada K, Kato M, Kiyama H

    Neuroscience   Vol. 351   page: 15-23   2017

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

  9. ECEL1 mutation implicates impaired axonal arborization of motor nerves in the pathogenesis of distal arthrogryposis Reviewed

    Nagata K, Kiryu-Seo S, Tamada H, Okuyama-Uchimura F, Kiyama H, Saido TC

    Acta Neuropathol   Vol. 132 ( 1 ) page: 111-126   2016

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

  10. Motor nerve arborization requires proteolytic domain of Damage-induced neuronal endopeptidase (DINE) during development Reviewed

    Matsumoto S, Kiryu-Seo S, Kiyama H

    J Neurosci   Vol. 36 ( 17 ) page: 4744-4757   2016

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

    DOI: 10.1523/JNEUROSCI.3811-15.2016

  11. TREM2/DAP12 signal elicits pro-inflammatory response in microglia and exacerbates neuropathic pain Reviewed

    Kobayashi M, Konishi H, Sayo A, Takai T, Kiyama H

    J Neurosci   Vol. 36 ( 43 ) page: 11138-11150   2016

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

    DOI: 10.1523/JNEUROSCI.1238-16.2016

  12. Mitochondrial fission is an acute response against injury-induced neurodegeneration Reviewed

    Kiryu-Seo S, Tamada H, Kato Y, Yasuda K, Ishihara N, Nomura M, Mihara K, Kiyama H

    Sci Rep   Vol. 6   page: 28331   2016

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

    DOI: 10.1038/srep28331

  13. Existence of c-Kit negative cells with ultrastructural features of interstitial cells of Cajal in the subserosal layer of the W/Wv mutant mouse colon Reviewed

    Tamada H, Kiyama H

    J Smooth Muscle Res.   Vol. 51   page: 1-9   2016

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

  14. Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS Reviewed

    Watanabe S, Ilieva H, Tamada H, Nomura H, Komine O, Endo F, Jin S, Mancias P, Kiyama H, Yamanaka K

    EMBO Mol Med   Vol. 8 ( 12 ) page: 1421-1437   2016

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

    DOI: 10.15252/emmm.201606403

  15. Increased a-series gangliosides positively regulate leptin/Ob receptor-mediated signals in hypothalamus of GD3 synthase-deficient mice Reviewed

    Ji S, Tokizane K, Ohkawa Y, Ohmi Y, BannoR, Okajima T, Kiyama H, Furuawa K, Furukawa K-I

    Biochem Biophys Res Commun   Vol. 479 ( 3 ) page: 453-460   2016

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

    DOI: 10.1016/j.bbrc.2016.09.077

  16. Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury Reviewed

    Jung J, Uesugi N, Jeong NJ, Park BS, Konishi H, Kiyama H

    Neuroscience   Vol. 313   page: 10-22   2016

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

    DOI: 10.1016/j.neuroscience.2015.11.028

  17. R-spondin 2 promotes acetylcholine receptor clustering at the neuromuscular junction via Lgr5 Reviewed

    Nakashima H, Ohkawara B, Ishigaki S, Fukudome T, Ito K, Tsushima M, Konishi H, Okuno T, Yoshimura T, Ito M, Masuda A, Sobue G, Kiyama H, Ishiguro N, Ohno K

    Sci Rep   Vol. 6   page: 28512   2016

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  18. Phenylbutazone induces expression of MBNL1 and suppresses formation of MBNL1-CUG RNA foci in a mouse model of myotonic dystrophy

    Chen G, Masuda A, Konishi H, Ohkawara B, Ito M, Kinoshita M, Kiyama H, Matsuura T, Ohno K

    Sci Rep   Vol. 2   page: 25317   2016

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

    DOI: 10.1038/srep25317

  19. Ontogeny and innervation of taste buds in mouse palatal gustatory epithelium Reviewed

    Rashwan A, Konishi H, El-Sharaby A, Kiyama H

    J Chemical Neuroanat   Vol. 71   page: 26-40   2016

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

    DOI: 10.1016/j.jchemneu.2015.11.003

  20. A DAP12-Dependent Signal Promotes Pro-Inflammatory Polarization in Microglia Following Nerve Injury and Exacerbates Degeneration of Injured Neurons Reviewed

    Kobayashi M, Konishi H, Takai T, Kiyama H

    Glia   Vol. 63 ( 6 ) page: 1073-1082   2015

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  21. Peripheral and spinal mechanisms of nociception in a rat reserpine-induced pain model Reviewed

    Taguchi T, Katanosaka T, Yasui M, Hayashi K, Yamashita M, Wakatsuki K, Kiyama H, Yamanaka A, Mizumura K

    Pain   Vol. 156 ( 3 ) page: 415-427   2015

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  22. Phagocytic astrocytes: Emerging from the shadows of microglia Invited Reviewed

    Konishi Hiroyuki, Koizumi Schuichi, Kiyama Hiroshi

    GLIA   Vol. 70 ( 6 ) page: 1009 - 1026   2022.6

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

    Elimination of dead or live cells take place in both a healthy and diseased central nervous system (CNS). Dying or dead cells are quickly cleared by phagocytosis for the maintenance of a healthy CNS or for recovery after injury. Live cells or parts thereof, such as the synapses and myelin, are appropriately eliminated by phagocytosis to maintain or refine neural networks during development and adulthood. Microglia, the specific population of resident macrophages in the CNS, are classically considered as primary phagocytes; however, astrocytes have also been highlighted as phagocytes in the last decade. Phagocytic targets and receptors are reported to be mostly common between astrocytes and microglia, which raises the question of how astrocytic phagocytosis differs from microglial phagocytosis, and how these two phagocytic systems cooperate. In this review, we address the consequences of astrocytic phagocytosis, particularly focusing on these elusive points.

    DOI: 10.1002/glia.24145

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  23. Axonal injury alters the extracellular glial environment of the axon initial segment and allows substantial mitochondrial influx into axon initial segment Invited Reviewed

    Tamada Hiromi, Kiryu-Seo Sumiko, Sawada Sohgo, Kiyama Hiroshi

    JOURNAL OF COMPARATIVE NEUROLOGY   Vol. 529 ( 16 ) page: 3621 - 3632   2021.11

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Journal of Comparative Neurology  

    The axon initial segment (AIS) is structurally and functionally distinct from other regions of the axon, yet alterations in the milieu of the AIS after brain injury have not been well characterized. In this study, we have examined extracellular and intracellular changes in the AIS after hypoglossal nerve injury. Microglial adhesions to the AIS were rarely observed in healthy controls, whereas microglial adhesions to the AIS became apparent in the axonal injury model. Regarding intra-AIS morphology, we focused on mitochondria because mitochondrial flow into the injured axon appears critical for axonal regeneration. To visualize mitochondria specifically in injured axons, we used Atf3:BAC transgenic mice whose mitochondria were labeled with GFP in response to nerve injury. These mice clearly showed mitochondrial localization in the AIS after nerve injury. To precisely confirm the light microscopic observations, we performed three-dimensional ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM). Although the healthy AIS was not surrounded by microglia, tight microglial adhesions with thick processes adhering to the AIS were observed after injury. FIB/SEM simultaneously allowed the observation of mitochondrial localization in the AIS. In the AIS of non-injured neurons, few mitochondria were observed, whereas mitochondria were abundantly localized in the cell body, axon hillock, and axon. Intriguingly, in the injured AIS, numerous mitochondria were observed throughout the AIS. Taken together, axonal injury changes the extracellular glial environment surrounding the AIS and intracellular mitochondrial localization in the AIS. These changes would be crucial responses, perhaps for injured neurons to regenerate after axonal injury.

    DOI: 10.1002/cne.25212

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  24. A mouse model of microglia-specific ablation in the embryonic central nervous system. Invited Reviewed

    Li C, Konishi H, Nishiwaki K, Sato K, Miyata T, Kiyama H

    Neuroscience research     2021.6

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

    Microglia, which migrate into the central nervous system (CNS) during the early embryonic stages, are considered to play various roles in CNS development. However, their embryonic roles are largely unknown, partly due to the lack of an effective microglial ablation system in the embryo. Here, we show a microglial ablation model by injecting diphtheria toxin (DT) into the amniotic fluid of Siglechdtr mice, in which the gene encoding DT receptor is knocked into the microglia-specific gene locus Siglech. We revealed that embryonic microglia were depleted for several days throughout the CNS, including some regions where microglia transiently accumulated, at any embryonic time point from embryonic day 10.5, when microglia colonize the CNS. This ablation system was specific for microglia because CNS-associated macrophages, which are a distinct population from microglia that reside in the CNS interfaces such as meninges, were unaffected. Therefore, this microglial ablation system is highly effective for studying the embryonic functions of microglia.

    DOI: 10.1016/j.neures.2021.06.002

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  25. TC10, a Rho family GTPase, is required for efficient axon regeneration in a neuron-autonomous manner Invited Reviewed

    Koinuma Shingo, Negishi Ryota, Nomura Riko, Sato Kazuki, Kojima Takuya, Segi-Nishida Eri, Goitsuka Ryo, Iwakura Yoichiro, Wada Naoyuki, Koriyama Yoshiki, Kiryu-Seo Sumiko, Kiyama Hiroshi, Nakamura Takeshi

    JOURNAL OF NEUROCHEMISTRY   Vol. 157 ( 4 ) page: 1196 - 1206   2021.5

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Journal of Neurochemistry  

    Intracellular signaling pathways that promote axon regeneration are closely linked to the mechanism of neurite outgrowth. TC10, a signaling molecule that acts on neurite outgrowth through membrane transport, is a member of the Rho family G proteins. Axon injury increases the TC10 levels in motor neurons, suggesting that TC10 may be involved in axon regeneration. In this study, we tried to understand the roles of TC10 in the nervous system using TC10 knock-out mice. In cultured hippocampal neurons, TC10 ablation significantly reduced axon elongation without affecting ordinary polarization. We determined a role of TC10 in microtubule stabilization at the growth cone neck; therefore, we assume that TC10 limits axon retraction and promotes in vitro axon outgrowth. In addition, there were no notable differences in the size and structure of brains during prenatal and postnatal development between wild-type and TC10 knock-out mice. In motor neurons, axon regeneration after injury was strongly suppressed in mice lacking TC10 (both in conventional and injured nerve specific deletion). In retinal ganglion cells, TC10 ablation suppressed the axon regeneration stimulated by intraocular inflammation and cAMP after optic nerve crush. These results show that TC10 plays an important role in axon regeneration in both the peripheral and central nervous systems, and the role of TC10 in peripheral axon regeneration is neuron-intrinsic. (Figure presented.).

    DOI: 10.1111/jnc.15235

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  26. Morphology, localization, and postnatal development of dural macrophages Invited Reviewed

    Sato Takehito, Konishi Hiroyuki, Tamada Hiromi, Nishiwaki Kimitoshi, Kiyama Hiroshi

    CELL AND TISSUE RESEARCH   Vol. 384 ( 1 ) page: 49 - 58   2021.4

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Cell and Tissue Research  

    The dura mater contains abundant macrophages whose functions remain largely elusive. Recent studies have demonstrated the origin, as well as the gene expression pattern, of dural macrophages (dMΦs). However, their histological features have not been explored yet. In this study, we performed immunohistochemistry and electron microscopy to elucidate their precise morphology, localization, and postnatal development in mice. We found that the morphology, as well as the localization, of dMΦs changed during postnatal development. In neonatal mice, dMΦ exhibited an amoeboid morphology. During postnatal development, their cell bodies elongated longitudinally and became aligned along dural blood vessels. In adulthood, nearly half of the dMΦs aligned along blood vessel networks. However, most of these cells were not directly attached to vessels; pericytes and fibroblasts interposed between dMΦs and vessels. This morphological information may provide further indications for the functional significance of dMΦs.

    DOI: 10.1007/s00441-020-03346-y

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  27. Zonisamide ameliorates neuropathic pain partly by suppressing microglial activation in the spinal cord in a mouse model Invited Reviewed

    Koshimizu Hiroyuki, Ohkawara Bisei, Nakashima Hiroaki, Ota Kyotaro, Kanbara Shunsuke, Inoue Taro, Tomita Hiroyuki, Sayo Akira, Kiryu-Seo Sumiko, Konishi Hiroyuki, Ito Mikako, Masuda Akio, Ishiguro Naoki, Imagama Shiro, Kiyama Hiroshi, Ohno Kinji

    LIFE SCIENCES   Vol. 263   page: 118577   2020.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Life Sciences  

    Neuropathic pain is caused by a lesion or a functional impairment of the sensory nervous system and allodynia is one of the frequently observed symptoms in neuropathic pain. Allodynia represents abnormal pain due to a non-noxious stimulus that does not normally provoke pain. Cellular mechanisms underlying neuropathic pain remain mostly elusive, and partial pain relief can be achieved in a limited number of patients by antidepressants, anticonvulsants topical anesthetics, and others. Zonisamide (ZNS) is widely used as an anti-epileptic and anti-Parkinson's disease drug. A recent report shows that ZNS suppresses neuropathic pain associated with diabetes mellitus in a mouse model. We made a mouse model of neuropathic pain in the hindlimb by cutting the nerve at the intervertebral canal at lumbar level 4 (L4). At 28 days after nerve injury, ZNS ameliorated allodynic pain, and reduced the expression of inflammatory cytokines and the nerve injury-induced increase of Iba1-positive microglia in the spinal dorsal horn at L4. In BV2 microglial cells, ZNS reduced the number of lipopolysaccharide-induced amoeboid-shaped cells, representing activated microglia. These results suggest that ZNS is a potential therapeutic agent for neuropathic pain partly by suppressing microglia-mediated neuroinflammation.

    DOI: 10.1016/j.lfs.2020.118577

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  28. Non-pathological roles of microglial TREM2/DAP12: TREM2/DAP12 regulates the physiological functions of microglia from development to aging Invited Reviewed

    Konishi Hiroyuki, Kiyama Hiroshi

    NEUROCHEMISTRY INTERNATIONAL   Vol. 141   page: 104878   2020.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Neurochemistry International  

    Triggering receptor expressed on myeloid cells 2 (TREM2) forms a receptor complex with DNAX-activating protein of 12 kDa (DAP12) on the microglial plasma membrane. A wide variety of protein and non-protein ligands, including lipids and DNA, can bind to TREM2, inducing the activation of microglia via DAP12. Both Trem2 and Dap12 have been identified as causative genes for Nasu-Hakola disease, which causes presenile dementia in association with bone cysts. Furthermore, TREM2/DAP12 signaling represents an essential inducer of the activated microglial phenotype in neuronal diseases, including Alzheimer's disease. Therefore, most previous studies examining TREM2/DAP12 have focused on their roles in microglia under pathological conditions. However, a growing body of evidence has demonstrated the involvement of TREM2/DAP12 signaling in the regulation of physiological functions in microglia. Accordingly, by examining the importance of TREM2/DAP12 in the regulation of microglial activity during development, homeostasis, and aging in the brain, this review elucidates the roles played by this complex in the healthy brain.

    DOI: 10.1016/j.neuint.2020.104878

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  29. Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction Invited Reviewed

    Konishi Hiroyuki, Okamoto Takayuki, Hara Yuichiro, Komine Okiru, Tamada Hiromi, Maeda Mitsuyo, Osako Fumika, Kobayashi Masaaki, Nishiyama Akira, Kataoka Yosky, Takai Toshiyuki, Udagawa Nobuyuki, Jung Steffen, Ozato Keiko, Tamura Tomohiko, Tsuda Makoto, Yamanaka Koji, Ogi Tomoo, Sato Katsuaki, Kiyama Hiroshi

    EMBO JOURNAL   Vol. 39 ( 22 ) page: e104464   2020.11

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:EMBO Journal  

    Microglia are the principal phagocytes that clear cell debris in the central nervous system (CNS). This raises the question, which cells remove cell debris when microglial phagocytic activity is impaired. We addressed this question using Siglechdtr mice, which enable highly specific ablation of microglia. Non-microglial mononuclear phagocytes, such as CNS-associated macrophages and circulating inflammatory monocytes, did not clear microglial debris. Instead, astrocytes were activated, exhibited a pro-inflammatory gene expression profile, and extended their processes to engulf microglial debris. This astrocytic phagocytosis was also observed in Irf8-deficient mice, in which microglia were present but dysfunctional. RNA-seq demonstrated that even in a healthy CNS, astrocytes express TAM phagocytic receptors, which were the main astrocytic phagocytic receptors for cell debris in the above experiments, indicating that astrocytes stand by in case of microglial impairment. This compensatory mechanism may be important for the maintenance or prolongation of a healthy CNS.

    DOI: 10.15252/embj.2020104464

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  30. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation Invited Reviewed

    Haruwaka Koichiro, Ikegami Ako, Tachibana Yoshihisa, Ohno Nobuhiko, Konishi Hiroyuki, Hashimoto Akari, Matsumoto Mami, Kato Daisuke, Ono Riho, Kiyama Hiroshi, Moorhouse Andrew J., Nabekura Junichi, Wake Hiroaki

    NATURE COMMUNICATIONS   Vol. 10 ( 1 ) page: 5816   2019.12

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Nature Communications  

    Microglia survey brain parenchyma, responding to injury and infections. Microglia also respond to systemic disease, but the role of blood–brain barrier (BBB) integrity in this process remains unclear. Using simultaneous in vivo imaging, we demonstrated that systemic inflammation induces CCR5-dependent migration of brain resident microglia to the cerebral vasculature. Vessel-associated microglia initially maintain BBB integrity via expression of the tight-junction protein Claudin-5 and make physical contact with endothelial cells. During sustained inflammation, microglia phagocytose astrocytic end-feet and impair BBB function. Our results show microglia play a dual role in maintaining BBB integrity with implications for elucidating how systemic immune-activation impacts neural functions.

    DOI: 10.1038/s41467-019-13812-z

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  31. The Link between Type III Reg and STAT3-Associated Cytokines in Inflamed Colonic Tissues Invited Reviewed

    Xu Xin, Fukui Hirokazu, Ran Ying, Wang Xuan, Inoue Yoshihito, Ebisudani Nobuhiko, Nishimura Heihachiro, Tomita Toshihiko, Oshima Tadayuki, Watari Jiro, Kiyama Hiroshi, Miwa Hiroto

    MEDIATORS OF INFLAMMATION   Vol. 2019   page: 7859460   2019.11

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Mediators of Inflammation  

    Reg (regenerating gene) family proteins are known to be overexpressed in gastrointestinal (GI) tissues under conditions of inflammation. However, the pathophysiological significance of Reg family protein overexpression and its regulation is still unclear. In the present study, we investigated the profile of Reg family gene expression in a colitis model and focused on the regulation of Reg IIIβ and IIIγ, which are overexpressed in inflamed colonic mucosa. C57BL/6 mice were administered 2% dextran sulfate sodium (DSS) in drinking water for five days, and their colonic tissues were investigated histopathologically at interval for up to 12 weeks. Gene expression of the Reg family and cytokines (IL-6, IL-17, and IL-22) was evaluated by real-time RT-PCR, and Reg IIIβ/γ expression was examined by immunohistochemistry. The effects of cytokines on STAT3 phosphorylation and HIP/PAP (type III REG) expression in Caco2 and HCT116 cells were examined by Western blot analysis. Among Reg family genes, Reg IIIβ and IIIγ were alternatively overexpressed in the colonic tissues of mice with DSS-induced colitis. The expression of STAT3-associated cytokines (IL-6, IL-17, and IL-22) was also significantly increased in those tissues, being significantly correlated with that of Reg IIIβ/γ. STAT3 phosphorylation and HIP/PAP expression were significantly enhanced in Caco2 cells upon stimulation with IL-6, IL-17, and IL-22. In HCT116 cells, those enhancements were also observed by IL-6 and IL-22 stimulations but not IL-17. The link between type III Reg and STAT3-associated cytokines appears to play a pivotal role in the pathophysiology of DSS-induced colitis.

    DOI: 10.1155/2019/7859460

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  32. Dual Microglia Effects on Blood Brain Barrier Permeability Induced by Systemic Inflammation Invited Reviewed

    Haruwaka K, Ikegami A, Tachibana Y, Ohno N, Konishi H, Hashimoto A, Matsumoto M, Kato D, Ono R, Kiyama H, Moorhouse A, Nabekura J, and Wake H

    Nat Commun     2019.11

  33. Dual functions of microglia in the formation and refinement of neural circuits during development. Invited Reviewed

    Konishi H, Kiyama H, Ueno M

    International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience   Vol. 77   page: 18 - 25   2019.10

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

    DOI: 10.1016/j.ijdevneu.2018.09.009

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  34. Astrocytic phagocytosis as a compensated function of microglial dysfunction Invited Reviewed

    Konishi H., Kiyama H.

    GLIA   Vol. 67   page: E534 - E534   2019.7

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  35. New Insights of a Neuronal Peptidase DINE/ECEL1: Nerve Development, Nerve Regeneration and Neurogenic Pathogenesis Invited Reviewed

    Kiryu-Seo Sumiko, Nagata Kenichi, Saido Takaomi C., Kiyama Hiroshi

    NEUROCHEMICAL RESEARCH   Vol. 44 ( 6 ) page: 1279 - 1288   2019.6

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    Our understanding of the physiological relevance of unique Damage-induced neuronal endopeptidase (DINE) [also termed Endothelin-converting enzyme-like 1 (ECEL1)] has recently expanded. DINE/ECEL1 is a type II membrane-bound metalloprotease, belonging to a family including the neprilysin (NEP) and endothelin-converting enzyme (ECE). The family members degrade and/or process peptides such as amyloid β and big-endothelins, which are closely associated with pathological conditions. Similar to NEP and ECE, DINE has been expected to play an important role in injured neurons as well as in developing neurons, because of its remarkable transcriptional response to neuronal insults and predominant neuronal expression from the embryonic stage. However, the physiological significance of DINE has long remained elusive. In the last decade, a series of genetically manipulated mice have driven research progress to elucidate the physiological aspects of DINE. The mice ablating Dine fail to arborize the embryonic motor axons in some subsets of muscles, including the respiratory muscles, and die immediately after birth. The abnormal phenotype of motor axons is also caused by one amino acid exchanges of DINE/ECEL1, which are responsible for distal arthrogryposis type 5 in a group of human congenital movement disorders. Furthermore, the mature Dine-deficient mice in which the lethality is rescued by genetic manipulation have shown the involvement of DINE in central nervous system regeneration. Here we describe recent research advances that DINE-mediated proteolytic processes are critical for nerve development, regeneration and pathogenesis, and discuss the future potential for DINE as a therapeutic target for axonal degeneration/disorder.

    DOI: 10.1007/s11064-018-2665-x

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  36. Necroptosis of Intestinal Epithelial Cells Induces Type 3 Innate Lymphoid Cell-Dependent Lethal Ileitis Invited Reviewed

    Shindo Ryodai, Ohmuraya Masaki, Komazawa-Sakon Sachiko, Miyake Sanae, Deguchi Yutaka, Yamazaki Soh, Nishina Takashi, Yoshimoto Takayuki, Kakuta Soichiro, Koike Masato, Uchiyama Yasuo, Konishi Hiroyuki, Kiyama Hiroshi, Mikami Tetuo, Moriwaki Kenta, Araki Kimi, Nakano Hiroyasu

    ISCIENCE   Vol. 15   page: 536 - +   2019.5

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    Immunology; Immune Response; Cell Biology; Functional Aspects of Cell Biology

    DOI: 10.1016/j.isci.2019.05.011

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  37. GPR34 in spinal microglia exacerbates neuropathic pain in mice Invited Reviewed

    Sayo Akira, Konishi Hiroyuki, Kobayashi Masaaki, Kano Kuniyuki, Kobayashi Hiroki, Hibi Hideharu, Aoki Junken, Kiyama Hiroshi

    JOURNAL OF NEUROINFLAMMATION   Vol. 16 ( 1 ) page: 82   2019.4

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    Background: Neuropathic pain is caused by sensory nerve injury, but effective treatments are currently lacking. Microglia are activated in the spinal dorsal horn after sensory nerve injury and contribute to neuropathic pain. Accordingly, molecules expressed by these cells are considered potential targets for therapeutic strategies. Our previous gene screening study using a mouse model of motor nerve injury showed that the G-protein-coupled receptor 34 gene (GPR34) is induced by nerve injury. Because GPR34 is now considered a microglia-enriched gene, we explored the possibility that it might be involved in microglial activation in the dorsal horn in a mouse model of neuropathic pain. Methods: mRNA expression of GPR34 and pro-inflammatory molecules was determined by quantitative real-time PCR in wild-type and GPR34-deficient mice with L4 spinal nerve injury. In situ hybridization was used to identify GPR34 expression in microglia, and immunohistochemistry with the microglial marker Iba1 was performed to examine microglial numbers and morphology. Mechanical sensitivity was evaluated by the von Frey hair test. Liquid chromatography-tandem mass spectrometry quantified expression of the ligand for GPR34, lysophosphatidylserine (LysoPS), in the dorsal horn, and a GPR34 antagonist was intrathecally administrated to examine the effect of inhibiting LysoPS-GPR34 signaling on mechanical sensitivity. Results: GPR34 was predominantly expressed by microglia in the dorsal horn after L4 nerve injury. There were no histological differences in microglial numbers or morphology between WT and GPR34-deficient mice. However, nerve injury-induced pro-inflammatory cytokine expression levels in microglia and pain behaviors were significantly attenuated in GPR34-deficient mice. Furthermore, the intrathecal administration of the GPR34 antagonist reduced neuropathic pain. Conclusions: Inhibition of GPR34-mediated signal by GPR34 gene deletion reduced nerve injury-induced neuropathic pain by suppressing pro-inflammatory responses of microglia without affecting their morphology. Therefore, the suppression of GPR34 activity may have therapeutic potential for alleviating neuropathic pain.

    DOI: 10.1186/s12974-019-1458-8

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  38. Hyperactivation of proprioceptors induces microglia-mediated long-lasting pain in a rat model of chronic fatigue syndrome Invited Reviewed

    Yasui Masaya, Menjyo Yuki, Tokizane Kyohei, Shiozawa Akiko, Tsuda Makoto, Inoue Kazuhide, Kiyama Hiroshi

    JOURNAL OF NEUROINFLAMMATION   Vol. 16 ( 1 ) page: 67   2019.3

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    Background: Patients diagnosed with chronic fatigue syndrome (CFS) or fibromyalgia experience chronic pain. Concomitantly, the rat model of CFS exhibits microglial activation in the lumbar spinal cord and pain behavior without peripheral tissue damage and/or inflammation. The present study addressed the mechanism underlying the association between pain and chronic stress using this rat model. Methods: Chronic or continuous stress-loading (CS) model rats, housed in a cage with a thin level of water (1.5 cm in depth), were used. The von Frey test and pressure pain test were employed to measure pain behavior. The neuronal and microglial activations were immunohistochemically demonstrated with antibodies against ATF3 and Iba1. Electromyography was used to evaluate muscle activity. Results: The expression of ATF3, a marker of neuronal hyperactivity or injury, was first observed in the lumbar dorsal root ganglion (DRG) neurons 2 days after CS initiation. More than 50% of ATF3-positive neurons simultaneously expressed the proprioceptor markers TrkC or VGluT1, whereas the co-expression rates for TrkA, TrkB, IB4, and CGRP were lower than 20%. Retrograde labeling using fluorogold showed that ATF3-positive proprioceptive DRG neurons mainly projected to the soleus. Substantial microglial accumulation was observed in the medial part of the dorsal horn on the fifth CS day. Microglial accumulation was observed around a subset of motor neurons in the dorsal part of the ventral horn on the sixth CS day. The motor neurons surrounded by microglia were ATF3-positive and mainly projected to the soleus. Electromyographic activity in the soleus was two to three times higher in the CS group than in the control group. These results suggest that chronic proprioceptor activation induces the sequential activation of neurons along the spinal reflex arc, and the neuronal activation further activates microglia along the arc. Proprioceptor suppression by ankle joint immobilization significantly suppressed the accumulation of microglia in the spinal cord, as well as the pain behavior. Conclusion: Our results indicate that proprioceptor-induced microglial activation may be a key player in the initiation and maintenance of abnormal pain in patients with CFS.

    DOI: 10.1186/s12974-019-1456-x

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  39. Mitochondrial behavior during axon regeneration/degeneration in vivo. Invited Reviewed

    Kiryu-Seo S, Kiyama H

    Neuroscience research   Vol. 139   page: 42 - 47   2019.2

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    DOI: 10.1016/j.neures.2018.08.014

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  40. Branched Sialylated N-glycans Are Accumulated in Brain Synaptosomes and Interact with Siglec-H. Invited Reviewed

    Handa-Narumi M, Yoshimura T, Konishi H, Fukata Y, Manabe Y, Tanaka K, Bao GM, Kiyama H, Fukase K, Ikenaka K

    Cell structure and function   Vol. 43 ( 2 ) page: 141 - 152   2018.8

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    DOI: 10.1247/csf.18009

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  41. Microglial TREM2/DAP12 Signaling: A Double-Edged Sword in Neural Diseases Invited Reviewed

    Konishi Hiroyuki, Kiyama Hiroshi

    FRONTIERS IN CELLULAR NEUROSCIENCE   Vol. 12   page: 206   2018.8

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    DOI: 10.3389/fncel.2018.00206

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  42. Complete adult neurogenesis within a Wallerian degenerating nerve expressed as an ectopic ganglion Invited Reviewed

    Nakano Tomonori, Kurimoto Shigeru, Kato Shuichi, Asano Kenichi, Hirata Takuma, Kiyama Hiroshi, Hirata Hitoshi

    JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE   Vol. 12 ( 6 ) page: 1469 - 1480   2018.6

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    DOI: 10.1002/term.2679

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  43. Lack of Fgf18 causes abnormal clustering of motor nerve terminals at the neuromuscular junction with reduced acetylcholine receptor clusters Invited Reviewed

    Ito Kenyu, Ohkawara Bisei, Yagi Hideki, Nakashima Hiroaki, Tsushima Mikito, Ota Kyotaro, Konishi Hiroyuki, Masuda Akio, Imagama Shiro, Kiyama Hiroshi, Ishiguro Naoki, Ohno Kinji

    SCIENTIFIC REPORTS   Vol. 8 ( 1 ) page: 434   2018.1

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    DOI: 10.1038/s41598-017-18753-5

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  44. Collapse of mitochondria-associated membrane as common pathomechanism for amyotrophic lateral sclerosis

    Watanabe S., Ilieva H., Tamada H., Nomura H., Komine O., Endo F., Jin S., Mancias P., Kiyama H., Yamanaka K.

    JOURNAL OF THE NEUROLOGICAL SCIENCES   Vol. 381   page: 104-104   2017.10

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    DOI: 10.1016/j.jns.2017.08.334

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  45. Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM Invited Reviewed

    Tamada Hiromi, Kiryu-Seo Sumiko, Hosokawa Hiroki, Ohta Keisuke, Ishihara Naotada, Nomura Masatoshi, Mihara Katsuyoshi, Nakamura Kei-ichiro, Kiyama Hiroshi

    JOURNAL OF COMPARATIVE NEUROLOGY   Vol. 525 ( 11 ) page: 2535 - 2548   2017.8

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    DOI: 10.1002/cne.24213

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  46. Damage-induced neuronal endopeptidase (DINE) enhances axonal regeneration potential of retinal ganglion cells after optic nerve injury Invited Reviewed

    Kaneko Aoi, Kiryu-Seo Sumiko, Matsumoto Sakiko, Kiyama Hiroshi

    CELL DEATH & DISEASE   Vol. 8 ( 6 ) page: e2847   2017.6

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

    DOI: 10.1038/cddis.2017.212

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  47. Phospholipid re-localization induces microglial ramification Invited Reviewed

    Tokizane K., Konishi H., Makide K., Kawana H., Nakamuta S., Kaibuchi K., Ohwada T., Aoki J., Kiyama H.

    GLIA   Vol. 65   page: E156 - E157   2017.6

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  48. EXPOSURE TO DIPHTHERIA TOXIN IMPAIRS BOTH INNER AND OUTER DURING THE JUVENILE PERIOD HAIR CELLS IN C57BL/6 MICE Invited Reviewed

    Konishi Hiroyuki, Ohgami Nobutaka, Matsushita Aika, Kondo Yuki, Aoyama Yuki, Kobayashi Masaaki, Nagai Taku, Ugawa Shinya, Yamada Akiyofumi, Kato Masashi, Kiyama Hiroshi

    NEUROSCIENCE   Vol. 351   page: 15 - 23   2017.5

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    DOI: 10.1016/j.neuroscience.2017.03.028

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  49. Phospholipid localization implies microglial morphology and function via Cdc42 in vitro Invited Reviewed

    Tokizane Kyohei, Konishi Hiroyuki, Makide Kumiko, Kawana Hiroki, Nakamuta Shinichi, Kaibuchi Kozo, Ohwada Tomohiko, Aoki Junken, Kiyama Hiroshi

    GLIA   Vol. 65 ( 5 ) page: 740 - 755   2017.5

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    DOI: 10.1002/glia.23123

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  50. Effects of Nutritional Supplementation on Fatigue, and Autonomic and Immune Dysfunction in Patients with End-Stage Renal Disease: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial Reviewed

    Fukuda S, Koyama H, Kondo K, Fujii H, Hirayama Y, Tabata T, Okamura M, Yamakawa T, Okada S, Hirata S, Kiyama H, Kajimoto O, Watanabe Y, Inaba M, Nishizawa Y

    PLoS One   Vol. 10 ( 3 ) page: e0119578   2015

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  51. Beta-series gangliosides crucially regulate leptin secretion in adipose tissues

    Shuting Ji, Ohkawa Y, Tokizane K, Ohmi Y, Banno R, FurukawaK, Kiyama H, Furukawa K

    Biochem Biophys Res Commun   Vol. 459 ( 2 ) page: 189-195   2015

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  52. microRNA-124 is down regulated in nerve injured motor neurons and it potentially targets mRNAs for KLF6 and STAT3 Reviewed

    Nagata K, Hama I, Kiryu-Seo S and Kiyama H

    Neuroscience   Vol. 256   page: 426-432   2014

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  53. Interferon regulatory factor 8 expressed in microglia contributes to tactile allodynia induced by repeated cold stress in rodents Reviewed

    Akagi T, Matsumura Y, Yasui M, Minami E, Inoue H, Masuda T, Tozaki-Saitoh H, Tamura T, Mizumura K, Tsuda M, Kiyama H, Inoue K

      Vol. 126 ( 2 ) page: 172-176   2014

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  54. Down-regulation of KCC2 expression and phosphorylation in motoneurons, and increases the number of in primary afferent projections to motoneurons in mice with post-stroke spasticity Reviewed

    Toda T, Ishida K, Kiyama H, Yamashita T, Lee S

    PLoS One   Vol. 9 ( 12 ) page: e114328   2014

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  55. A chronic fatigue syndrome model demonstrates mechanical allodynia and muscular hyperalgesia via spinal microglial activation

    Yasui M, Yoshimura T, Takeuchi S, Tokizane K, Tsuda M, Inoue K, Kiyama H

    Glia   Vol. 62 ( 9 ) page: 1407-1417   2014

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  56. Weakened rate-dependent depression of Hoffmann's reflex and increased motoneuron hyperactivity after motor cortical infarction in mice

    Lee S, TodaT, Kiyama H, and Yamashita T

    Cell Death & Disease   Vol. 5   page: e1007   2014

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  57. Continuous stress promotes expression of VGF in melanotroph via suppression of dopamine Reviewed

    Tokizane K, Konishi H, Yasui M, Ogawa T, Sasaki K, Minamino N, Kiyama H

    Mol Cell Endocrinol   Vol. 372 ( 1-2 ) page: 49-56   2013

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  58. Differential induction of antimicrobial REGIII by intestinal microbiota and Bifidobacterium breve NCC2950 Reviewed

    Natividad MMJ, Hayes C, Motta J-P, Jury J, Galipeau HJ, Philip V, Rodenas CG, Kiyama H, Bercik P, and Verdu EF

    Appl Environ Microbiol   Vol. 79 ( 24 ) page: 7745-7754   2013

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  59. Damage-induced neuronal endopeptidase is critical for presynaptic formation of neuro-muscular junctions Reviewed

    Nagata K, Kiryu-Seo S, Maeda M, Yoshida K, Morita T, Kiyama H

    J Neurosci.   Vol. 30 ( 20 ) page: 6954-6962   2010

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  60. Neuronal injury-inducible gene is synergistically regulated by ATF3, cJun and STAT3 through the interaction with Sp1 in damaged neurons Reviewed

    Kiryu-Seo S, Kato R, Ogawa T, Nakagomi S, Nagata K, Kiyama H

    J Biol Chem   Vol. 283 ( 11 ) page: 6988-6996   2008

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  61. Identification of peripherin as a novel Akt substrate in neurons Reviewed

    Konishi H, Namikawa K, Shikata K, Kobatake Y, Tachibana T, Kiyama H

    J Biol Chem   Vol. 282 ( 32 ) page: 23491-23499   2007

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  62. Pancreatitis-associated protein-III (PAP-III) is a novel macrophage chemoattractant implicated in nerve regeneration Reviewed

    Namikawa K, Okamoto T, Suzuki A, Konishi H, Kiyama H

    J Neurosci   Vol. 26 ( 28 ) page: 7460-7467   2006

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  63. Unique anti-apoptotic activity of EAAC1 in injured motor neurons Reviewed

    Kiryu-Seo S, Gamo K, Tachibana T, Tanaka K, Kiyama H

    EMBO J   Vol. 25 ( 14 ) page: 3411-3421   2006

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  64. Noxa is a critical mediator of p53-dependent motor neuron death after nerve injury in adult mouse. Reviewed

    Kiryu-Seo S, Hirayama T, Kato R, Kiyama H

    J Neurosci   Vol. 25 ( 6 ) page: 1442-1447   2005

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  65. Expression of the Activating transcription factor 3 (ATF3) prevents JNK-induced neuronal death by promoting Hsp27 expression and Akt activation Reviewed

    Nakagomi S, Suzuki Y, Namikawa K, Kiryu-Seo S, Kiyama H

    J Neuosci   Vol. 23 ( 12 ) page: 5187-5196   2003

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  66. Akt / Protein kinase B prevents injury-induced motor neuron death and accelerates axonal regeneration Reviewed

    Namikawa K, Honma M, Abe K, Takeda M, Mansur K, Obata t, Miwa A, Okado H, Kiyama H

      Vol. 20   page: 2875-2886   2000

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  67. Damage induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers. Reviewed

    Proc. Natl. Acad. Sci. USA   Vol. 97   page: 4345-4350   2000

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  68. The small GTP-binding protein TC10 promotes growth cone-like formation and nerve elongation in neuronal cells, and its expression is induced during nerve regeneration in rats. Reviewed

    Tanabe K, Tachibana T, Yamashita T, Che YH, Yoneda Y, Ochi T, Tohyama M, Yoshikawa T, Kiyama H

      Vol. 20   page: 4138-4144   2000

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  69. Accelerated nerve regeneration in mice by upregulated expression of IL-6 and IL-6 receptor after trauma. Reviewed

      Vol. 183   page: 2627-2634   1996

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  70. p53 independent cyclin G expression in a group of mature neurons and its enhanced expression during nerve regeneration. Reviewed

    Morita N, Kiryu S, Kiyama H

      Vol. 16   page: 5961-5966   1996

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  71. Nerve injury enhances rat neuronal glutamate transporter expression: identification by differential display PCR. Reviewed

    Kiryu S, Yao GL, Morita N, Kato H, Kiyama H

    J Neurosci.   Vol. 15   page: 7872-7878   1995.10

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▼display all

Books 4

  1. 筋骨格系の解剖アトラス 上肢編

    木山博資、一柳雅仁( Role: Supervisor (editorial))

    金芳堂  2020.4  ( ISBN:ISBN978-4-7653-1818-1

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    Total pages:262   Language:Japanese Book type:Textbook, survey, introduction

  2. 人体の解剖生理学

    木山博資, 遠山正彌( Role: Joint editor)

    金芳堂  2017.4  ( ISBN:978-4-7635-1709-2

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    Language:Japanese Book type:Textbook, survey, introduction

  3. 神経科学研究の最先端プロトコールI.分子組織化学

    塩坂貞夫(編集)木山博資(編集)( Role: Edit)

    厚生社  1994.3 

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    Language:Japanese Book type:Scholarly book

  4. バイオマニュアルシリーズ9「蛋白質核酸分子のin situ 同定法」

    遠山正彌、塩坂貞夫、木山博資( Role: Joint editor)

    羊土社  1994 

Presentations 4

  1. A new horizon in nerve regeneration research -Consequences of interactions between neuron and non-neuronal cells in nerve regeneration- Invited International conference

    Kiyama H

    EURO-Japan International Workshop 

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    Event date: 2017.1

    Language:English   Presentation type:Oral presentation (keynote)  

    Venue:Kyoto   Country:Japan  

  2. Lipids regulate microglial morphology and function Invited International conference

    Kiyama H

    Cold Spring Harbor Asia Conferences, Novel insights into Glia function & Dysfunction 

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    Event date: 2016.12

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Suzhou, China   Country:Japan  

  3. The mitochondrial dynamics after nerve injury Invited International conference

    Kiryu-Seo S and Kiyama H

    25th International Society for Neurochemistry (ISN) 

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    Event date: 2015.8

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Cairns Australia   Country:Australia  

  4. Microglia as a fate determinant of injured neurons invited speaker Invited International conference

    Kiyama H

    Cold Spring Harbor Asia Conferences 

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    Event date: 2015.6

    Language:English   Presentation type:Symposium, workshop panel (nominated)  

    Venue:Suzhou, China   Country:China  

KAKENHI (Grants-in-Aid for Scientific Research) 7

  1. 慢性的なストレス負荷による新たなミクログリア作動原理の解明

    2013.4 - 2015.3

    科学研究費補助金 

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    Authorship:Principal investigator 

  2. 脳内免疫担当細胞ミクログリアを主軸とする慢性難治性疼痛発症メカニズムの解明

    2011.4 - 2015.3

    科学研究費補助金  CREST

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    Authorship:Coinvestigator(s) 

  3. 固有感覚異常を標的としたリハビリテーションによる脳内炎症緩和をめざす基礎研究

    Grant number:22H03437  2022.4 - 2025.3

    科学研究費助成事業  基盤研究(B)

    木山 博資

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    Authorship:Principal investigator 

    Grant amount:\17420000 ( Direct Cost: \13400000 、 Indirect Cost:\4020000 )

  4. Roles of lipid signaling and remodeling in nerve injury

    Grant number:19H03395  2019.4 - 2022.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Authorship:Principal investigator 

    Grant amount:\17160000 ( Direct Cost: \13200000 、 Indirect Cost:\3960000 )

  5. 損傷神経の生存軸索再生を制御するスクラップ&ビルドの分子基盤の解明

    Grant number:17H05743  2017.4 - 2019.3

    新学術領域研究(研究領域提案型)

    木山 博資

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    Authorship:Principal investigator 

    Grant amount:\11050000 ( Direct Cost: \8500000 、 Indirect Cost:\2550000 )

    昨年度はSiglec-Hが脳内のミクログリアにのみ発現し、脳常在性マクロファージには発現しないことを明らかにし、Siglec-Hの遺伝子にジフテリア毒素受容体を組み込んだマウスを用いることにより、ミクログリアを特異的に除去できることを示した。このノックインマウス(Siglec-H-DTR)では従来のIba1遺伝子やプロモーターを利用したミクログリア操作マウスよりはミクログリア特異性という点で優れている。これを用いることによりマクロファージとミクログリアの機能の違いやお互いの相互作用の研究に発展させることが可能になると考えられる。脳内ではミクログリアが主要な貪食能を有する細胞なので、ミクログリア自身がジフテリアトキシンによって細胞死に至った時に、どのようにしてミクログリアが除去(スクラップ)されるか検討した。脳内でミクログリアが特異的に障害されたとき、GFAPの発現上昇をともなってアストロサイトの活性化が観察された。また、ミクログリアの残骸がアストロサイトに貪食されている像も観察された。このことから、普段は貪食能を有しないアストロサイトが、ミクログリアが存在しない条件下では、代償的に貪食能を発揮することが明らかになった。このような代償性貪食が、より生理的な条件下でも生じるかどうかは検討中である。現時点ではアストロサイトの代償性貪食機能の作動機序は不明であるが、アストロサイトには従来から知られている機能に加え、新たにスクラッパーとしての機能が存在することが示された。
    平成30年度が最終年度であるため、記入しない。
    平成30年度が最終年度であるため、記入しない。

  6. Organelle dynamics for fate determination of injured neurons

    Grant number:16H05117  2016.4 - 2019.3

    Kiyama Hiroshi

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    Authorship:Principal investigator 

    Grant amount:\17550000 ( Direct Cost: \13500000 、 Indirect Cost:\4050000 )

    We have investigated significances of organelle dynamics which are observed in response to nerve injury. We used the BAC transgenic mice, which express mitochondria labelling GFP and Cre recombinase protein simultaneously and specifically in nerve injured neurons in response to nerve injury. After nerve injury the mitochondria in injured nerve became smaller and moved quicker, although the mitochondrial size in cell soma was not changed. This morphological alteration of mitochondria would be important for delivering mitochondria to regenerating nerve tip. The deletion of Dpr1, which is a responsible molecule for the mitochondrial fission, induced mitochondrial enlargement, and the Drp1 deleted motor neurons died quickly in response to nerve injury.

  7. Mechanism underlying chronic pain seen in the animal model for the chronic fatigue syndrome

    Grant number:16K15170  2016.4 - 2018.3

    Kiyama Hiroshi

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    Authorship:Principal investigator 

    Grant amount:\3640000 ( Direct Cost: \2800000 、 Indirect Cost:\840000 )

    Our previous study using animal model for chronic fatigue syndrome (CFS) suggested that the pain observed in patients with CFS and fibromyalgia syndrome (FMS) involves microglial activation, and therefore in the present study, we investigated the mechanism underlying the pain. Our results suggested that the stress loading elicits continuous and specific hyper-activation of proprioceptors in the dorsal root ganglia, and the hyper-activated signal triggers microglial activation in the specific regions of spinal cord. These activated regions locate along the spinal reflex arc, and the activated microglia along the arc thereby inducing prolonged and abnormal levels of pain. The results indicate that proprioceptor-induced microglial activation may be crucial in the initiation and maintenance of abnormal pain in patients with CFS.

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Teaching Experience (On-campus) 17

  1. 人体器官の構造(組織学)講義・実習

    2021

  2. 人体器官の構造(肉眼解剖学)講義・実習

    2021

  3. 基礎医学セミナー

    2021

  4. Seminar for Functional Histology

    2021

  5. Experimental Research on Functional Histology

    2021

  6. Brain Morphology

    2021

  7. 医工連携セミナー

    2021

  8. 人体器官の構造(組織学)講義・実習

    2019

  9. 修士講義

    2019

  10. 基礎セミナーA

    2019

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    ゼミ形式

  11. 基礎医学セミナー

    2019

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    医学研究法の指導、論文作成

  12. 神経解剖学

    2019

  13. 人体器官の構造(肉眼解剖学)講義・実習

    2019

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    講義と実習

  14. 基礎セミナーA

    2015

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    ゼミ形式

  15. 自然環境と人間

    2015

  16. 基礎セミナーA

    2012

  17. First Year Seminar B

    2011

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Social Contribution 6

  1. J Neurochemistry (Handling Editor)

    2000.10 - 2013.12

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    Handling Editor

  2. J Chemical Neuroanatomy (Editor)

    2013.10

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    編集委員 Editor

  3. Anatomical Science International (Managing Editor)

    2015.4

  4. 自律神経 (編集委員)

    2013.1

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    雑誌「自律神経」編集委員

  5. 人体解剖トレーニングセミナー  実行委員長

    2011.8

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    医育機関の解剖教育担当者の解剖トレーニング
    実行委員長

  6. 中学校講演会

    2013.11

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    富山市立山室中学で生徒父兄対象に講演した。

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