2024/10/18 更新

写真a

モリ ダイスケ
森 大輔
DAISUKE Mori
所属
脳とこころの研究センター 研究開発部門 特任准教授
職名
特任准教授

学位 1

  1. 博士(理学) ( 2003年3月   東北大学 ) 

研究キーワード 10

  1. 脳・神経

  2. 統合失調症

  3. 細胞内輸送

  4. 神経細胞

  5. 発達障害

  6. 極性

  7. 包括脳ネットワーク

  8. プロテオーム

  9. シグナル伝達

  10. ゴルジ体

研究分野 2

  1. ライフサイエンス / 医化学  / 精神医学

  2. ライフサイエンス / 分子生物学

経歴 1

  1. 名古屋大学   脳とこころの研究センター   特任准教授

    2016年6月 - 現在

学歴 2

  1. 東北大学   大学院理学系研究科   化学専攻博士課程

  2. 東北大学   大学院理学系研究科   化学専攻修士課程

所属学協会 2

  1. 日本神経科学会

  2. 日本分子生物学会

 

論文 52

  1. ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk 査読有り

    Mariko Sekiguchi, Akira Sobue, Itaru Kushima, Chenyao Wang, Yuko Arioka, Hidekazu Kato, Akiko Kodama, Hisako Kubo, Norimichi Ito, Masahito Sawahata, Kazuhiro Hada, Ryosuke Ikeda, Mio Shinno, Chikara Mizukoshi, Keita Tsujimura, Akira Yoshimi, Kanako Ishizuka, Yuto Takasaki, Hiroki Kimura, Jingrui Xing, Yanjie Yu, Maeri Yamamoto, Takashi Okada, Emiko Shishido, Toshiya Inada, Masahiro Nakatochi, Tetsuya Takano, Keisuke Kuroda, Mutsuki Amano, Branko Aleksic, Takashi Yamomoto, Tetsushi Sakuma, Tomomi Aida, Kohichi Tanaka, Ryota Hashimoto, Makoto Arai, Masashi Ikeda, Nakao Iwata, Teppei Shimamura, Taku Nagai, Toshitaka Nabeshima, Kozo Kaibuchi, Kiyofumi Yamada, Daisuke Mori, Norio Ozaki

    Translational Psychiatry   10 巻 ( 1 )   2020年12月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    DOI: 10.1038/s41398-020-00917-z

    その他リンク: http://www.nature.com/articles/s41398-020-00917-z

  2. Generation of induced pluripotent stem cells from a schizophrenia patient with heterozygous 1q21.1 deletion. 国際誌

    Hiroki Okumura, Yu Hayashi, Yuko Arioka, Itaru Kushima, Daisuke Mori, Norio Ozaki

    Stem cell research   81 巻   頁: 103555 - 103555   2024年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    1q21.1 deletion has been identified as a risk factor related to not only mental disorders such as schizophrenia, but also congenital heart defects. However, at human cellular and molecular levels, it is still not known how this variant affects brain and heart development and contributes to the onset of these diseases. Here, we generated induced pluripotent stem cells (iPSCs) from a patient with 1q21.1 deletion. The iPSCs expressed stemness markers and exhibited the ability to differentiate into three germ layers in vitro. These iPSCs will be useful tools to understand the pathophysiology of mental disorders and heart defects in humans.

    DOI: 10.1016/j.scr.2024.103555

    PubMed

  3. Analysis of human neuronal cells carrying ASTN2 deletion associated with psychiatric disorders. 国際誌

    Yu Hayashi, Hiroki Okumura, Yuko Arioka, Itaru Kushima, Daisuke Mori, Tzuyao Lo, Gantsooj Otgonbayar, Hidekazu Kato, Yoshihiro Nawa, Hiroki Kimura, Branko Aleksic, Norio Ozaki

    Translational psychiatry   14 巻 ( 1 ) 頁: 236 - 236   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Recent genetic studies have found common genomic risk variants among psychiatric disorders, strongly suggesting the overlaps in their molecular and cellular mechanism. Our research group identified the variant in ASTN2 as one of the candidate risk factors across these psychiatric disorders by whole-genome copy number variation analysis. However, the alterations in the human neuronal cells resulting from ASTN2 variants identified in patients remain unknown. To address this, we used patient-derived and genome-edited iPS cells with ASTN2 deletion; cells were further differentiated into neuronal cells. A comprehensive gene expression analysis using genome-edited iPS cells with variants on both alleles revealed that the expression level of ZNF558, a gene specifically expressed in human forebrain neural progenitor cells, was greatly reduced in ASTN2-deleted neuronal cells. Furthermore, the expression of the mitophagy-related gene SPATA18, which is repressed by ZNF558, and mitophagy activity were increased in ASTN2-deleted neuronal cells. These phenotypes were also detected in neuronal cells differentiated from patient-derived iPS cells with heterozygous ASTN2 deletion. Our results suggest that ASTN2 deletion is related to the common pathogenic mechanism of psychiatric disorders by regulating mitophagy via ZNF558.

    DOI: 10.1038/s41398-024-02962-4

    PubMed

  4. Extremely Low Frequency, Extremely Low Magnetic Environment for depression: An open-label trial. 国際誌

    Masako Tachibana, Toshiya Inada, Hiroki Kimura, Mikako Ito, Yachiyo Kuwatsuka, Fumie Kinoshita, Daisuke Mori, Kinji Ohno

    Asian journal of psychiatry   96 巻   頁: 104036 - 104036   2024年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Mitochondrial dysfunction has been suggested to play a role in depression pathogenesis. This clinical trial (jRCTs042220011) was conducted to evaluate whether depression symptoms could be alleviated by an Extremely Low Frequency, Extremely Low Magnetic Environment (ELF-ELME), which has been found in basic research studies to enhance mitochondrial membrane potential. Participants were exposed to the ELF-ELME via a head-mounted magnetic field device (10 μTesla, 4 ms, 1-8 Hz/8 s) worn for 2 h per day for 8 consecutive weeks. Four male patients with treatment-resistant depression were enrolled. Significant reductions from baseline in the average total Montgomery-Åsberg Depression Rating Scale (MADRS) score were observed at 4, 6, and 8 weeks. ELF-ELME appears to ameliorate depressive symptoms in patients with major depressive disorder safely and effectively, suggesting that it could be used as an alternative treatment for depressive patients who do not prefer to take antidepressants and in combination with antidepressant therapy for patients who only partially respond to pharmacotherapy.

    DOI: 10.1016/j.ajp.2024.104036

    PubMed

  5. Phenotypes for general behavior, activity, and body temperature in 3q29 deletion model mice

    Daisuke Mori, Ryosuke Ikeda, Masahito Sawahata, Sho Yamaguchi, Akiko Kodama, Takashi Hirao, Yuko Arioka, Hiroki Okumura, Chihiro Inami, Toshiaki Suzuki, Yu Hayashi, Hidekazu Kato, Yoshihiro Nawa, Seiko Miyata, Hiroki Kimura, Itaru Kushima, Branko Aleksic, Hiroyuki Mizoguchi, Taku Nagai, Takanobu Nakazawa, Ryota Hashimoto, Kozo Kaibuchi, Kazuhiko Kume, Kiyofumi Yamada, Norio Ozaki

    Translational Psychiatry   14 巻 ( 1 )   2024年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    Abstract

    Whole genome analysis has identified rare copy number variations (CNV) that are strongly involved in the pathogenesis of psychiatric disorders, and 3q29 deletion has been found to have the largest effect size. The 3q29 deletion mice model (3q29-del mice) has been established as a good pathological model for schizophrenia based on phenotypic analysis; however, circadian rhythm and sleep, which are also closely related to neuropsychiatric disorders, have not been investigated. In this study, our aims were to reevaluate the pathogenesis of 3q29-del by recreating model mice and analyzing their behavior and to identify novel new insights into the temporal activity and temperature fluctuations of the mouse model using a recently developed small implantable accelerometer chip, Nano-tag. We generated 3q29-del mice using genome editing technology and reevaluated common behavioral phenotypes. We next implanted Nano-tag in the abdominal cavity of mice for continuous measurements of long-time activity and body temperature. Our model mice exhibited weight loss similar to that of other mice reported previously. A general behavioral battery test in the model mice revealed phenotypes similar to those observed in mouse models of schizophrenia, including increased rearing frequency. Intraperitoneal implantation of Nano-tag, a miniature acceleration sensor, resulted in hypersensitive and rapid increases in the activity and body temperature of 3q29-del mice upon switching to lights-off condition. Similar to the 3q29-del mice reported previously, these mice are a promising model animals for schizophrenia. Successive quantitative analysis may provide results that could help in treating sleep disorders closely associated with neuropsychiatric disorders.

    DOI: 10.1038/s41398-023-02679-w

    その他リンク: https://www.nature.com/articles/s41398-023-02679-w

  6. Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

    Daisuke Mori, Chihiro Inami, Ryosuke Ikeda, Masahito Sawahata, Shinji Urata, Sho Yamaguchi, Yohei Kobayashi, Kosuke Fujita, Yuko Arioka, Hiroki Okumura, Itaru Kushima, Akiko Kodama, Toshiaki Suzuki, Takashi Hirao, Akira Yoshimi, Akira Sobue, Takahiro Ito, Yukihiro Noda, Hiroyuki Mizoguchi, Taku Nagai, Kozo Kaibuchi, Shigeo Okabe, Koji Nishiguchi, Kazuhiko Kume, Kiyofumi Yamada, Norio Ozaki

        2024年1月

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  7. Assessing the Real-World, Long-Term Impact of Lemborexant on Sleep Quality in a Home-Based Clinical Study. 国際誌

    Seiko Miyata, Kunihiro Iwamoto, Ippei Okada, Akihiro Fujimoto, Yuki Kogo, Daisuke Mori, Manabu Amano, Nao Matsuyama, Kazuki Nishida, Masahiko Ando, Toshiaki Taoka, Shinji Naganawa, Norio Ozaki

    Nature and science of sleep   16 巻   頁: 291 - 303   2024年

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    記述言語:英語  

    PURPOSE: Both subjective and objective evaluations are essential for the treatment of insomnia. Lemborexant has been shown to be effective in the long-term based solely on a subjective basis, and no long-term objective measures have been evaluated under natural sleep conditions. Small, lightweight sleep electroencephalogram (EEG) monitor was used, instead of polysomnography, to objectively evaluate sleep at home 4 and 12 weeks after lemborexant treatment. PATIENTS AND METHODS: Adults and elderly subjects with insomnia disorder, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were enrolled in this open-label, single-arm, single-center trial. Objective and subjective measures of sleep were prospectively assessed. Sleep disturbance, excessive sleepiness, and depressive symptoms were assessed using questionnaires. RESULTS: A total of 45 subjects were screened, of which 33 were enrolled. Paired t-tests were conducted to evaluate changes in sleep variables and compared with the baseline; subjects showed significant improvements in objective sleep efficiency (SE) and subjective sleep parameters at weeks 4 and 12 following treatment with lemborexant. When baseline values were taken into account, a repeated-multivariate analysis of variance (MANOVA) revealed statistically significant changes in the objective measures. Sleep disturbance, excessive sleepiness, and depressive symptoms improved after three months of lemborexant treatment. CONCLUSION: Furthermore, lemborexant therapy improved nocturnal sleep, when measured objectively using sleep EEG monitoring at home, and improved daytime sleepiness and depressive symptoms in older adults with insomnia disorder.

    DOI: 10.2147/NSS.S448871

    PubMed

  8. Histological Analysis of a Mouse Model of the 22q11.2 Microdeletion Syndrome

    Hidenori Tabata, Daisuke Mori, Tohru Matsuki, Kaichi Yoshizaki, Masato Asai, Atsuo Nakayama, Norio Ozaki, Koh-ichi Nagata

    Biomolecules   13 巻 ( 5 ) 頁: 763 - 763   2023年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:MDPI AG  

    22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of developing various psychiatric and developmental disorders, including schizophrenia and early-onset Parkinson’s disease. Recently, a mouse model of this disease, Del(3.0Mb)/+, mimicking the 3.0 Mb deletion which is most frequently found in patients with 22q11.2DS, was generated. The behavior of this mouse model was extensively studied and several abnormalities related to the symptoms of 22q11.2DS were found. However, the histological features of their brains have been little addressed. Here we describe the cytoarchitectures of the brains of Del(3.0Mb)/+ mice. First, we investigated the overall histology of the embryonic and adult cerebral cortices, but they were indistinguishable from the wild type. However, the morphologies of individual neurons were slightly but significantly changed from the wild type counterparts in a region-specific manner. The dendritic branches and/or dendritic spine densities of neurons in the medial prefrontal cortex, nucleus accumbens, and primary somatosensory cortex were reduced. We also observed reduced axon innervation of dopaminergic neurons into the prefrontal cortex. Given these affected neurons function together as the dopamine system to control animal behaviors, the impairment we observed may explain a part of the abnormal behaviors of Del(3.0Mb)/+ mice and the psychiatric symptoms of 22q11.2DS.

    DOI: 10.3390/biom13050763

  9. Analysis of human neuronal cells carrying ASTN2 deletion: A cross-disorder risk variant of schizophrenia, autism spectrum disorder, and bipolar disorder

    Yuko Arioka, Yu Hayashi, Hiroki Okumura, Itaru Kushima, Daisuke Mori, Tzuyao Lo, Gantsooj Otgonbayar, Hidekazu Kato, Yoshihiro Nawa, Hiroki Kimura, Branko Aleksic, Norio Ozaki

        2023年2月

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  10. Inhibition of Rho-kinase ameliorates decreased spine density in the medial prefrontal cortex and methamphetamine-induced cognitive dysfunction in mice carrying schizophrenia-associated mutations of the Arhgap10 gene 査読有り

    Rinako Tanaka, Jingzhu Liao, Kazuhiro Hada, Daisuke Mori, Taku Nagai, Tetsuo Matsuzaki, Toshitaka Nabeshima, Kozo Kaibuchi, Norio Ozaki, Hiroyuki Mizoguchi, Kiyofumi Yamada

    Pharmacological Research   187 巻   頁: 106589 - 106589   2023年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.phrs.2022.106589

  11. Rho-kinase 2選択的阻害剤は日本人統合失調症患者で見つかった<i>Arhgap10</i>遺伝子バリアントを有するマウスの内側前頭前皮質のスパイン密度低下を改善する

    田中 里奈子, 朱 文俊, 森 大輔, 毛利 彰宏, 永井 拓, 鍋島 俊隆, 貝淵 弘三, 橘 大輝, 小林 洋平, 尾崎 紀夫, 溝口 博之, 山田 清文

    日本薬理学会年会要旨集   97 巻   頁: 1-B-YIA2-5   2023年

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    記述言語:日本語   出版者・発行元:公益社団法人 日本薬理学会  

    Copy number variants in the<i> ARHGAP10</i> gene are associated with schizophrenia (SCZ). We have previously demonstrated that Rho-kinase (ROCK) inhibitor, fasudil, ameliorates the decreased spine density in the medial prefrontal cortex (mPFC) of <i>Arhgap10 </i>S490P/NHEJ<i> </i>mice carrying the variants that mimic the <i>ARHGAP10</i> variants found in a Japanese SCZ patient. Accordingly, we have proposed that ROCK is a potentially novel therapeutic target in SCZ. It is well known that there are two subtypes of ROCK, ROCK1 and ROCK2, and that fasudil inhibits both subtypes. Since ROCK2 is highly expressed in the brain, here we evaluated the effect of a selective ROCK2 inhibitor, belumosudil (KD025), on spine density in <i>Arhgap10 S490P/NHEJ </i>mice. We measured the spine density of pyramidal neurons in layer 2/3 of the mPFC in <i>Arhgap10 </i>S490P/NHEJ<i> </i>mice following daily oral administration of KD025 for one week. Moreover, we evaluated the general behaviors in an open field and systolic blood pressure after KD025 treatment. KD025 ameliorated decreased spine density of cortical neurons in the mPFC of <i>Arhgap10 </i>S490P/NHEJ<i> </i>mice, but had little effects on general behaviors and systolic blood pressure induced by fasudil. These observations suggest that ROCK2 is a more appropriate therapeutic target in SCZ, with little inducibility of hypotension.

    DOI: 10.1254/jpssuppl.97.0_1-b-yia2-5

  12. Establishment of induced pluripotent stem cells from a patient with 16p13.11 duplication and VPS13B deletion. 国際誌

    Hiroki Okumura, Yuko Arioka, Itaru Kushima, Daisuke Mori, Norio Ozaki

    Stem cell research   64 巻   頁: 102884 - 102884   2022年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    VPS13B deletion and 16p13.11 duplication are related to mental disorders, such as schizophrenia. However, how these variants affect human neurons and contribute to the development of mental disorders is yet to be elucidated. In this study, we generated induced pluripotent stem cells (iPSCs) from a patient with 16p13.11 duplication and VPS13B deletion. The iPSCs indicated pluripotency marker expression and the differentiation capacity into three germ layers in vitro. Therefore, these iPSC lines will be useful tools to further understand the pathophysiology of mental disorders.

    DOI: 10.1016/j.scr.2022.102884

    PubMed

  13. Functional connector hubs in the cerebellum. 国際誌

    Kazuya Kawabata, Epifanio Bagarinao, Hirohisa Watanabe, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Reiko Ohdake, Michihito Masuda, Aya Ogura, Toshiyasu Kato, Shuji Koyama, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Norio Ozaki, Gen Sobue

    NeuroImage   257 巻   頁: 119263 - 119263   2022年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Accumulating evidence from anatomical and neuroimaging studies suggests that the cerebellum is engaged in a variety of motor and cognitive tasks. Given its various functions, a key question is whether the cerebellum also plays an important role in the brain's integrative functions. Here, we hypothesize the existence of connector regions, also known as connector hubs, where multiple resting state networks converged in the cerebellum. To verify this, we employed a recently developed voxel-level network measure called functional connectivity overlap ratio (FCOR), which could be used to quantify the spatial extent of a region's connection to several large-scale cortical networks. Using resting state functional MRI data from 101 healthy participants, cerebellar FCOR maps were constructed and used to identify the locations of connector hubs in the cerebellum. Results showed that a number of cerebellar regions exhibited strong connectivity with multiple functional networks, verifying our hypothesis. These highly connected regions were located in the posterior cerebellum, especially in lobules VI, VII, and IX, and mainly connected to the core neurocognitive networks such as default mode and executive control networks. Regions associated with the sensorimotor network were also localized in lobule V, VI, and VIII, albeit in small clusters. These cerebellar connector hubs may play an essential role in the processing of information across the core neurocognitive networks.

    DOI: 10.1016/j.neuroimage.2022.119263

    PubMed

  14. Investigation of OLIG2 as a candidate gene for schizophrenia and autism spectrum disorder.

    Sho Furuta, Branko Aleksic, Yoshihiro Nawa, Hiroki Kimura, Itaru Kushima, Kanako Ishizuka, Hidekazu Kato, Miho Toyama, Yuko Arioka, Daisuke Mori, Mako Morikawa, Toshiya Inada, Norio Ozaki

    Nagoya journal of medical science   84 巻 ( 2 ) 頁: 260 - 268   2022年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A number of genomic mutations that are thought to be strongly involved in the development of schizophrenia (SCZ) and autism spectrum disorder (ASD) have been identified. Abnormalities involving oligodendrocytes have been reported in SCZ, and as a related gene, oligodendrocyte lineage transcription factor 2 (OLIG2) has been reported to be strongly associated with SCZ. In this study, based on the common disease-rare variant hypothesis, target sequencing of candidate genes was performed to identify rare mutations with a high effect size and the possibility that the identified mutations may increase the risks of SCZ and ASD in the Japanese population. In this study, the exon region of OLIG2 was targeted; 370 patients with SCZ and 192 with ASD were subjected to next-generation sequencing. As a result, one rare missense mutation (A33T) was detected. We used the Sanger method to validate this missense mutation with a low frequency (<1%), and then carried out a genetic association analysis involving 3299 unrelated individuals (1447 with SCZ, 380 with ASD, and 1472 healthy controls) to clarify whether A33T was associated with SCZ or ASD. A33T was not found in either case group, and in only one control. We did not find evidence that p.A33T is involved in the onset of ASD or SCZ; however, associations with this variant need to be evaluated in larger samples to confirm our results.

    DOI: 10.18999/nagjms.84.2.260

    PubMed

  15. Correction to: Oxytocin ameliorates impaired social behavior in a mouse model of 3q29 deletion syndrome. 国際誌

    Tomoya Takemoto, Masayuki Baba, Kazumasa Yokoyama, Kohei Kitagawa, Kazuki Nagayasu, Yukio Ago, Kaoru Seiriki, Atsuko Hayata-Takano, Atsushi Kasai, Daisuke Mori, Norio Ozaki, Kazuhiro Takuma, Ryota Hashimoto, Hitoshi Hashimoto, Takanobu Nakazawa

    Molecular brain   15 巻 ( 1 ) 頁: 34 - 34   2022年4月

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    記述言語:英語  

    DOI: 10.1186/s13041-022-00920-z

    PubMed

  16. Cross-disorder analysis of genic and regulatory copy number variations in bipolar disorder, schizophrenia, and autism spectrum disorder

    Itaru Kushima, Masahiro Nakatochi, Branko Aleksic, Takashi Okada, Hiroki Kimura, Hidekazu Kato, Mako Morikawa, Toshiya Inada, Kanako Ishizuka, Youta Torii, Yukako Nakamura, Satoshi Tanaka, Miho Imaeda, Nagahide Takahashi, Maeri Yamamoto, Kunihiro Iwamoto, Yoshihiro Nawa, Nanayo Ogawa, Shuji Iritani, Yu Hayashi, Tzuyao Lo, Gantsooj Otgonbayar, Sho Furuta, Nakao Iwata, Masashi Ikeda, Takeo Saito, Kohei Ninomiya, Tomo Okochi, Ryota Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Kenichiro Miura, Masanari Itokawa, Makoto Arai, Mitsuhiro Miyashita, Kazuya Toriumi, Kazutaka Ohi, Toshiki Shioiri, Kiyoyuki Kitaichi, Toshiyuki Someya, Yuichiro Watanabe, Jun Egawa, Tsutomu Takahashi, Michio Suzuki, Tsukasa Sasaki, Mamoru Tochigi, Fumichika Nishimura, Hidenori Yamasue, Hitoshi Kuwabara, Tomoyasu Wakuda, Takahiro A. Kato, Shigenobu Kanba, Hideki Horikawa, Masahide Usami, Masaki Kodaira, Kyota Watanabe, Takeo Yoshikawa, Tomoko Toyota, Shigeru Yokoyama, Toshio Munesue, Ryo Kimura, Yasuko Funabiki, Hirotaka Kosaka, Minyoung Jung, Kiyoto Kasai, Tempei Ikegame, Seiichiro Jinde, Shusuke Numata, Makoto Kinoshita, Tadafumi Kato, Chihiro Kakiuchi, Kazuhiro Yamakawa, Toshimitsu Suzuki, Naoki Hashimoto, Shuhei Ishikawa, Bun Yamagata, Shintaro Nio, Toshiya Murai, Shuraku Son, Yasuto Kunii, Hirooki Yabe, Masumi Inagaki, Yu-ichi Goto, Yuto Okumura, Tomoya Ito, Yuko Arioka, Daisuke Mori, Norio Ozaki

    Biological Psychiatry   92 巻 ( 5 ) 頁: 362 - 374   2022年4月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.biopsych.2022.04.003

  17. Oxytocin ameliorates impaired social behavior in a mouse model of 3q29 deletion syndrome. 国際誌

    Tomoya Takemoto, Masayuki Baba, Kazumasa Yokoyama, Kohei Kitagawa, Kazuki Nagayasu, Yukio Ago, Kaoru Seiriki, Atsuko Hayata-Takano, Atsushi Kasai, Daisuke Mori, Norio Ozaki, Kazuhiro Takuma, Ryota Hashimoto, Hitoshi Hashimoto, Takanobu Nakazawa

    Molecular brain   15 巻 ( 1 ) 頁: 26 - 26   2022年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by specific social symptoms, restricted interests, stereotyped repetitive behaviors, and delayed language development. The 3q29 microdeletion (3q29del), a recurrent copy number variant, confers a high risk for ASD and schizophrenia, and serves as an important pathological model for investigating the molecular pathogenesis of a large number of neurodevelopmental and psychiatric conditions. Recently, mouse models carrying a deletion of the chromosomal region corresponding to the human 3q29 region (Df/+ mice) were generated and demonstrated neurodevelopmental and psychiatric conditions associated behavioral abnormalities, pointing to the relevance of Df/+ mice as a model for these conditions with high construct and face validity. Currently, the molecular pathogenesis of these behavioral phenotypes in Df/+ mice remains unclear. The oxytocin (OXT) system plays a central role in social behavior across species and has a potential role in ASD. In this study, to elucidate the molecular mechanisms behind impaired social behavior in Df/+ mice, we investigated the possible involvement of OXT signaling in impaired social behavior in Df/+ mice. We demonstrated that OXT administration restored the impaired social behavior in Df/+ mice. We also demonstrated that the number of OXT-positive cells in the paraventricular nucleus (PVN) was significantly lower in Df/+ mice than in wild-type (WT) littermates. Consistent with this, the level of OXT peptide in the cerebral cortex of Df/+ mice was lower than in WT littermates. Our study may provide important insights into the molecular pathophysiological basis of neurodevelopmental and psychiatric conditions, including ASD.

    DOI: 10.1186/s13041-022-00915-w

    PubMed

  18. Identification of ultra-rare disruptive variants in voltage-gated calcium channel-encoding genes in Japanese samples of schizophrenia and autism spectrum disorder. 国際誌

    Chenyao Wang, Shin-Ichiro Horigane, Minoru Wakamori, Shuhei Ueda, Takeshi Kawabata, Hajime Fujii, Itaru Kushima, Hiroki Kimura, Kanako Ishizuka, Yukako Nakamura, Yoshimi Iwayama, Masashi Ikeda, Nakao Iwata, Takashi Okada, Branko Aleksic, Daisuke Mori, Takashi Yoshida, Haruhiko Bito, Takeo Yoshikawa, Sayaka Takemoto-Kimura, Norio Ozaki

    Translational psychiatry   12 巻 ( 1 ) 頁: 84 - 84   2022年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Several large-scale whole-exome sequencing studies in patients with schizophrenia (SCZ) and autism spectrum disorder (ASD) have identified rare variants with modest or strong effect size as genetic risk factors. Dysregulation of cellular calcium homeostasis might be involved in SCZ/ASD pathogenesis, and genes encoding L-type voltage-gated calcium channel (VGCC) subunits Cav1.1 (CACNA1S), Cav1.2 (CACNA1C), Cav1.3 (CACNA1D), and T-type VGCC subunit Cav3.3 (CACNA1I) recently were identified as risk loci for psychiatric disorders. We performed a screening study, using the Ion Torrent Personal Genome Machine (PGM), of exon regions of these four candidate genes (CACNA1C, CACNA1D, CACNA1S, CACNA1I) in 370 Japanese patients with SCZ and 192 with ASD. Variant filtering was applied to identify biologically relevant mutations that were not registered in the dbSNP database or that have a minor allele frequency of less than 1% in East-Asian samples from databases; and are potentially disruptive, including nonsense, frameshift, canonical splicing site single nucleotide variants (SNVs), and non-synonymous SNVs predicted as damaging by five different in silico analyses. Each of these filtered mutations were confirmed by Sanger sequencing. If parental samples were available, segregation analysis was employed for measuring the inheritance pattern. Using our filter, we discovered one nonsense SNV (p.C1451* in CACNA1D), one de novo SNV (p.A36V in CACNA1C), one rare short deletion (p.E1675del in CACNA1D), and 14 NSstrict SNVs (non-synonymous SNV predicted as damaging by all of five in silico analyses). Neither p.A36V in CACNA1C nor p.C1451* in CACNA1D were found in 1871 SCZ cases, 380 ASD cases, or 1916 healthy controls in the independent sample set, suggesting that these SNVs might be ultra-rare SNVs in the Japanese population. The neuronal splicing isoform of Cav1.2 with the p.A36V mutation, discovered in the present study, showed reduced Ca2+-dependent inhibition, resulting in excessive Ca2+ entry through the mutant channel. These results suggested that this de novo SNV in CACNA1C might predispose to SCZ by affecting Ca2+ homeostasis. Thus, our analysis successfully identified several ultra-rare and potentially disruptive gene variants, lending partial support to the hypothesis that VGCC-encoding genes may contribute to the risk of SCZ/ASD.

    DOI: 10.1038/s41398-022-01851-y

    PubMed

  19. Sequencing of selected chromatin remodelling genes reveals increased burden of rare missense variants in ASD patients from the Japanese population

    Tzuyao Lo, Itaru Kushima, Branko Aleksic, Hidekazu Kato, Yoshihiro Nawa, Yu Hayashi, Gantsooj Otgonbayar, Hiroki Kimura, Yuko Arioka, Daisuke Mori, Norio Ozaki

    International Review of Psychiatry   34 巻 ( 2 ) 頁: 154 - 167   2022年2月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Informa UK Limited  

    DOI: 10.1080/09540261.2022.2072193

  20. Reserve and maintenance in the aging brain: A longitudinal study of healthy older adults. 国際誌

    Epifanio Bagarinao, Hirohisa Watanabe, Satoshi Maesawa, Kazuya Kawabata, Kazuhiro Hara, Reiko Ohdake, Aya Ogura, Daisuke Mori, Noritaka Yoneyama, Kazunori Imai, Takamasa Yokoi, Toshiyasu Kato, Shuji Koyama, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Norio Ozaki, Gen Sobue

    eNeuro   9 巻 ( 1 )   2022年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The aging brain undergoes structural changes even in very healthy individuals. Quantifying these changes could help disentangle pathological changes from those associated with the normal human aging process. Using longitudinal MRI data from 227 carefully selected healthy human cohort with age ranging from 50 to 80 years old at baseline scan, we quantified age-related volumetric changes in the brain of healthy human older adults. Longitudinally, the rates of tissue loss in total gray matter (GM) and white matter were 2,497.5 mm3 per year and 2,579.8 mm3 per year, respectively. Across the whole brain, the rates of GM decline varied with regions in the frontal and parietal lobes having faster rates of decline, whereas some regions in the occipital and temporal lobes appeared relatively preserved. In contrast, cross sectional changes were mainly observed in the temporal-occipital regions. Similar longitudinal atrophic changes were also observed in subcortical regions including thalamus, hippocampus, putamen, and caudate, whereas the pallidum showed an increasing volume with age. Overall, regions maturing late in development (frontal, parietal) are more vulnerable to longitudinal decline, whereas those that fully mature in the early stage (temporal, occipital) are mainly affected by cross sectional changes in healthy older cohort. This may suggest that, for a successful healthy aging, the former needs to be maximally developed at an earlier age to compensate for the longitudinal decline later in life and the latter to remain relatively preserved even in old age, consistent with both concepts of reserve and brain maintenance.Significance StatementAging is associated with gray matter (GM) decline, yet some individuals tend to remain cognitively healthy even in advanced age. What differentiates the brains of "healthy agers" from those individuals who are prone to faster cognitive decline still remains unclear. Using longitudinal MRI data from a carefully selected cohort, we examined the brain aging characteristics of healthy agers. Our findings showed that, even in this population, frontal-parietal regions have faster longitudinal rate of GM decline, whereas some temporal-occipital regions appeared relatively preserved. These findings may suggest that, for a successful healthy aging, frontal-parietal regions need to be maximally developed to compensate for the longitudinal decline later in life and the temporal-occipital regions to remain relatively preserved even in old age.

    DOI: 10.1523/ENEURO.0455-21.2022

    PubMed

  21. Mice with exonic RELN deletion identified from a patient with schizophrenia have impaired visual discrimination learning and reversal learning in touchscreen operant tasks

    Jingzhu Liao, Geyao Dong, Bolati Wulaer, Masahito Sawahata, Hiroyuki Mizoguchi, Daisuke Mori, Norio Ozaki, Toshitaka Nabeshima, Taku Nagai, Kiyofumi Yamada

    Behavioural Brain Research   416 巻   頁: 113569 - 113569   2022年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.bbr.2021.113569

  22. <i>Arhgap10</i>遺伝子変異マウスの神経活動の解析にむけた<i>in vivo</i>カルシウムイメージング法の確立

    田中 里奈子, 羽田 和弘, 溝口 博之, 澤幡 雅仁, 永井 拓, 森 大輔, 鍋島 俊隆, 貝淵 弘三, 尾崎 紀夫, 山田 清文

    日本薬理学会年会要旨集   95 巻   頁: 2-P-168   2022年

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    記述言語:日本語   出版者・発行元:公益社団法人 日本薬理学会  

    Recently we have identified <i>Arhgap10</i> gene mutations in Japanese schizophrenia patients by the genome-wide CNV analysis. ARHGAP10 negatively regulates Rho family small GTPases that play roles in the regulation of spine morphology. We also found that <i>Arhgap10 </i>S490P/NHEJ mice which were generated to mimic the patient case were highly sensitive to methamphetamine (METH) and spine density of the secondary dendrites of medium spiny neurons (MSNs) in the striatum was increased in the mutant mice. Because spine density is well associated with neuronal activity, in this study we sought to establish wireless photometry system to measure Ca<sup>2+</sup> level in the striatal MSNs of <i>Arhgap10 </i>S490P/NHEJ<i> </i>mice.  Firstly, we measured the number of the c-Fos positive cells in the striatum of <i>Arhgap10 </i>S490P/NHEJ mice by immunohistochemistry 2 h after METH (0.3 mg/kg, i.p.) treatment. METH increased the number of c-Fos positive cells in the dorsomedial striatum in <i>Arhgap10 </i>S490P/NHEJ mice but not wild-type mice. We generated mice expressing selectivity GCaMP6 in dopamine D1 receptor-expressing MSNs (D1-MSNs) of the striatum by Cre-loxP system. In a mean while we inserted optic fiber and detected GCaMP6 signal of the striatal D1-MSNs in Drd1-Cre mice under a free moving condition. Treatment of METH (2 mg/kg, i.p.) increased Ca<sup>2+</sup> signal in striatal D1-MSNs as well as locomotor activity.

    DOI: 10.1254/jpssuppl.95.0_2-p-168

  23. Bridging large-scale cortical networks: Integrative and function-specific hubs in the thalamus. 国際誌

    Kazuya Kawabata, Epifanio Bagarinao, Hirohisa Watanabe, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Reiko Ohdake, Michihito Masuda, Aya Ogura, Toshiyasu Kato, Shuji Koyama, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Norio Ozaki, Gen Sobue

    iScience   24 巻 ( 10 ) 頁: 103106 - 103106   2021年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The thalamus is critical for the brain's integrative hub functions; however, the localization and characterization of the different thalamic hubs remain unclear. Using a voxel-level network measure called functional connectivity overlap ratio (FCOR), we examined the thalamus' association with large-scale resting-state networks (RSNs) to elucidate its connector hub roles. Connections to the core-neurocognitive networks were localized in the anterior and medial parts, such as the anteroventral and mediodorsal nuclei areas. Regions functionally connected to the sensorimotor network were distinctively located around the lateral pulvinar nucleus but to a limited extent. Prominent connector hubs include the anteroventral, ventral lateral, and mediodorsal nuclei with functional connections to multiple RSNs. These findings suggest that the thalamus, with extensive connections to most of the RSNs, is well placed as a critical integrative functional hub and could play an important role for functional integration facilitating brain functions associated with primary processing and higher cognition.

    DOI: 10.1016/j.isci.2021.103106

    PubMed

  24. Individual voxel-based morphometry adjusting covariates in multiple system atrophy. 国際誌

    Junya Ebina, Kazuhiro Hara, Hirohisa Watanabe, Kazuya Kawabata, Fumio Yamashita, Atsushi Kawaguchi, Yusuke Yoshida, Toshiyasu Kato, Aya Ogura, Michihito Masuda, Reiko Ohdake, Daisuke Mori, Satoshi Maesawa, Masahisa Katsuno, Osamu Kano, Gen Sobue

    Parkinsonism & related disorders   90 巻   頁: 114 - 119   2021年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    INTRODUCTION: This study aimed to evaluate whether novel individual voxel-based morphometry adjusting covariates (iVAC), such as age, sex, and total intracranial volume, could increase the accuracy of a diagnosis of multiple system atrophy (MSA) and enable the differentiation of MSA from Parkinson's disease (PD). METHODS: We included 53 MSA patients (MSA-C: 33, MSA-P: 20), 53 PD patients, and 189 healthy controls in this study. All participants underwent high-resolution T1-weighted imaging (WI) and T2-WI with a 3.0-T MRI scanner. We evaluated the occurrence of significant atrophic findings in the pons/middle cerebellar peduncle (MCP) and putamen on iVAC and compared these findings with characteristic changes on T2-WI. RESULTS: On iVAC, abnormal findings were observed in the pons/MCP of 96.2% of MSA patients and in the putamen of 80% of MSA patients; however, on T2-WI, they were both observed at a frequency of 60.4% in MSA patients. On iVAC, all but one MSA-P patient (98.1%) showed significant atrophic changes in the pons/MCP or putamen. By contrast, 69.8% of patients with MSA showed abnormal signal changes in the pons/MCP or putamen on T2-WI. iVAC yielded 95.0% sensitivity and 96.2% specificity for differentiating MSA-P from PD. CONCLUSION: iVAC enabled us to recognize the morphological characteristics of MSA visually and with high accuracy compared to T2-WI, indicating that iVAC is a potential diagnostic screening tool for MSA.

    DOI: 10.1016/j.parkreldis.2021.07.025

    PubMed

  25. Two novel mouse models mimicking minor deletions in 22q11.2 deletion syndrome revealed the contribution of each deleted region to psychiatric disorders. 国際誌

    Ryo Saito, Chika Miyoshi, Michinori Koebis, Itaru Kushima, Kazuki Nakao, Daisuke Mori, Norio Ozaki, Hiromasa Funato, Masashi Yanagisawa, Atsu Aiba

    Molecular brain   14 巻 ( 1 ) 頁: 68 - 68   2021年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    22q11.2 deletion syndrome (22q11.2DS) is a disorder caused by the segmental deletion of human chromosome 22. This chromosomal deletion is known as high genetic risk factors for various psychiatric disorders. The different deletion types are identified in 22q11.2DS patients, including the most common 3.0-Mb deletion, and the less-frequent 1.5-Mb and 1.4-Mb deletions. In previous animal studies of psychiatric disorders associated with 22q11.2DS mainly focused on the 1.5-Mb deletion and model mice mimicking the human 1.5-Mb deletion have been established with diverse genetic backgrounds, which resulted in the contradictory phenotypes. On the other hand, the contribution of the genes in 1.4-Mb region to psychiatric disorders is poorly understood. In this study, we generated two mouse lines that reproduced the 1.4-Mb and 1.5-Mb deletions of 22q11.2DS [Del(1.4 Mb)/+ and Del(1.5 Mb)/+] on the pure C57BL/6N genetic background. These mutant mice were analyzed comprehensively by behavioral tests, such as measurement of locomotor activity, sociability, prepulse inhibition and fear-conditioning memory. Del(1.4 Mb)/+ mice displayed decreased locomotor activity, but no abnormalities were observed in all other behavioral tests. Del(1.5 Mb)/+ mice showed reduction of prepulse inhibition and impairment of contextual- and cued-dependent fear memory, which is consistent with previous reports. Furthermore, apparently intact social recognition in Del(1.4 Mb)/+ and Del(1.5 Mb)/+ mice suggests that the impaired social recognition observed in Del(3.0 Mb)/+ mice mimicking the human 3.0-Mb deletion requires mutations both in 1.4-Mb and 1.5 Mb regions. Our previous study has shown that Del(3.0 Mb)/+ mice presented disturbance of behavioral circadian rhythm. Therefore, we further evaluated sleep/wakefulness cycles in Del(3.0 Mb)/+ mice by electroencephalogram (EEG) and electromyogram (EMG) recording. EEG/EMG analysis revealed the disturbed wakefulness and non-rapid eye moving sleep (NREMS) cycles in Del(3.0 Mb)/+ mice, suggesting that Del(3.0 Mb)/+ mice may be unable to maintain their wakefulness. Together, our mouse models deepen our understanding of genetic contributions to schizophrenic phenotypes related to 22q11.2DS.

    DOI: 10.1186/s13041-021-00778-7

    PubMed

  26. Analysis of Reelin signaling and neurodevelopmental trajectory in primary cultured cortical neurons with RELN deletion identified in schizophrenia

    Yumi Tsuneura, Masahito Sawahata, Norimichi Itoh, Ryoya Miyajima, Daisuke Mori, Takao Kohno, Mitsuharu Hattori, Akira Sobue, Taku Nagai, Hiroyuki Mizoguchi, Toshitaka Nabeshima, Norio Ozaki, Kiyofumi Yamada

    Neurochemistry International   144 巻   頁: 104954 - 104954   2021年3月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier {BV}  

    DOI: 10.1016/j.neuint.2020.104954

  27. Mice carrying a schizophrenia-associated mutation of the Arhgap10 gene are vulnerable to the effects of methamphetamine treatment on cognitive function: association with morphological abnormalities in striatal neurons. 国際誌

    Kazuhiro Hada, Bolati Wulaer, Taku Nagai, Norimichi Itoh, Masahito Sawahata, Akira Sobue, Hiroyuki Mizoguchi, Daisuke Mori, Itaru Kushima, Toshitaka Nabeshima, Norio Ozaki, Kiyofumi Yamada

    Molecular brain   14 巻 ( 1 ) 頁: 21 - 21   2021年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    We recently found a significant association between exonic copy-number variations in the Rho GTPase activating protein 10 (Arhgap10) gene and schizophrenia in Japanese patients. Special attention was paid to one patient carrying a missense variant (p.S490P) in exon 17, which overlapped with an exonic deletion in the other allele. Accordingly, we generated a mouse model (Arhgap10 S490P/NHEJ mice) carrying a missense variant and a coexisting frameshift mutation. We examined the spatiotemporal expression of Arhgap10 mRNA in the brain and found the highest expression levels in the cerebellum, striatum, and nucleus accumbens (NAc), followed by the frontal cortex in adolescent mice. The expression levels of phosphorylated myosin phosphatase-targeting subunit 1 and phosphorylated p21-activated kinases in the striatum and NAc were significantly increased in Arhgap10 S490P/NHEJ mice compared with wild-type littermates. Arhgap10 S490P/NHEJ mice exhibited a significant increase in neuronal complexity and spine density in the striatum and NAc. There was no difference in touchscreen-based visual discrimination learning between Arhgap10 S490P/NHEJ and wild-type mice, but a significant impairment of visual discrimination was evident in Arhgap10 S490P/NHEJ mice but not wild-type mice when they were treated with methamphetamine. The number of c-Fos-positive cells was significantly increased after methamphetamine treatment in the dorsomedial striatum and NAc core of Arhgap10 S490P/NHEJ mice. Taken together, these results suggested that schizophrenia-associated Arhgap10 gene mutations result in morphological abnormality of neurons in the striatum and NAc, which may be associated with vulnerability of cognition to methamphetamine treatment.

    DOI: 10.1186/s13041-021-00735-4

    PubMed

  28. Chromosome 22q11.2 deletion causes PERK-dependent vulnerability in dopaminergic neurons

    Yuko Arioka, Emiko Shishido, Itaru Kushima, Toshiaki Suzuki, Ryo Saito, Atsu Aiba, Daisuke Mori, Norio Ozaki

    EBioMedicine   63 巻   頁: 103138 - 103138   2021年1月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.ebiom.2020.103138

  29. Resting State Networks Related to the Maintenance of Good Cognitive Performance During Healthy Aging. 国際誌

    Satoshi Maesawa, Satomi Mizuno, Epifanio Bagarinao, Hirohisa Watanabe, Kazuya Kawabata, Kazuhiro Hara, Reiko Ohdake, Aya Ogura, Daisuke Mori, Daisuke Nakatsubo, Haruo Isoda, Minoru Hoshiyama, Masahisa Katsuno, Ryuta Saito, Norio Ozaki, Gen Sobue

    Frontiers in human neuroscience   15 巻   頁: 753836 - 753836   2021年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Purpose: Maintenance of cognitive performance is important for healthy aging. This study aims to elucidate the relationship between brain networks and cognitive function in subjects maintaining relatively good cognitive performance. Methods: A total of 120 subjects, with equal number of participants from each age group between 20 and 70 years, were included in this study. Only participants with Addenbrooke's Cognitive Examination - Revised (ACE-R) total score greater than 83 were included. Anatomical T1-weighted MR images and resting-state functional MR images (rsfMRIs) were taken from all participants using a 3-tesla MRI scanner. After preprocessing, several factors associated with age including the ACE-R total score, scores of five domains, sub-scores of ACE-R, and brain volumes were tested. Morphometric changes associated with age were analyzed using voxel based morphometry (VBM) and changes in resting state networks (RSNs) were examined using dual regression analysis. Results: Significant negative correlations with age were seen in the total gray matter volume (GMV, r = -0.58), and in the memory, attention, and visuospatial domains. Among the different sub-scores, the score of the delayed recall (DR) showed the highest negative correlation with age (r = -0.55, p < 0.001). In VBM analysis, widespread regions demonstrated negative correlation with age, but none with any of the cognitive scores. Quadratic approximations of cognitive scores as functions of age showed relatively delayed decline compared to total GMV loss. In dual regression analysis, some cognitive networks, including the dorsal default mode network, the lateral dorsal attention network, the right / left executive control network, the posterior salience network, and the language network, did not demonstrate negative correlation with age. Some regions in the sensorimotor networks showed positive correlation with the DR, memory, and fluency scores. Conclusion: Some domains of the cognitive test did not correlate with age, and even the highly correlated sub-scores such as the DR score, showed delayed decline compared to the loss of total GMV. Some RSNs, especially involving cognitive control regions, were relatively maintained with age. Furthermore, the scores of memory, fluency, and the DR were correlated with the within-network functional connectivity values of the sensorimotor network, which supported the importance of exercise for maintenance of cognition.

    DOI: 10.3389/fnhum.2021.753836

    PubMed

  30. Elucidation of molecular pathogenesis and drug development for psychiatric disorders from rare disease-susceptibility variants

    Hiroki Kimura, Daisuke Mori, Branko Aleksic, Norio Ozaki

    Neuroscience Research     2020年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier BV  

    DOI: 10.1016/j.neures.2020.11.008

  31. Functional characterization of rare NRXN1 variants identified in autism spectrum disorders and schizophrenia

    Kanako Ishizuka, Tomoyuki Yoshida, Takeshi Kawabata, Ayako Imai, Hisashi Mori, Hiroki Kimura, Toshiya Inada, Yuko Okahisa, Jun Egawa, Masahide Usami, Itaru Kushima, Mako Morikawa, Takashi Okada, Masashi Ikeda, Aleksic Branko, Daisuke Mori, Toshiyuki Someya, Nakao Iwata, Norio Ozaki

    Journal of Neurodevelopmental Disorders   12 巻 ( 1 )   2020年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>
    <sec>
    <title>Background</title>
    Rare genetic variants contribute to the etiology of both autism spectrum disorder (ASD) and schizophrenia (SCZ). Most genetic studies limit their focus to likely gene-disrupting mutations because they are relatively easier to interpret their effects on the gene product. Interpretation of missense variants is also informative to some pathophysiological mechanisms of these neurodevelopmental disorders; however, their contribution has not been elucidated because of relatively small effects. Therefore, we characterized missense variants detected in <italic>NRXN1</italic>, a well-known neurodevelopmental disease-causing gene, from individuals with ASD and SCZ.


    </sec>
    <sec>
    <title>Methods</title>
    To discover rare variants with large effect size and to evaluate their role in the shared etiopathophysiology of ASD and SCZ, we sequenced <italic>NRXN1</italic> coding exons with a sample comprising 562 Japanese ASD and SCZ patients, followed by a genetic association analysis in 4273 unrelated individuals. Impact of each missense variant detected here on cell surface expression, interaction with NLGN1, and synaptogenic activity was analyzed using an in vitro functional assay and in silico three-dimensional (3D) structural modeling.


    </sec>
    <sec>
    <title>Results</title>
    Through mutation screening, we regarded three ultra-rare missense variants (T737M, D772G, and R856W), all of which affected the LNS4 domain of <italic>NRXN1</italic>α isoform<italic>,</italic> as disease-associated variants. Diagnosis of individuals with T737M, D772G, and R856W was 1ASD and 1SCZ, 1ASD, and 1SCZ, respectively. We observed the following phenotypic and functional burden caused by each variant. (i) D772G and R856W carriers had more serious social disabilities than T737M carriers. (ii) In vitro assay showed reduced cell surface expression of NRXN1α by D772G and R856W mutations. In vitro functional analysis showed decreased NRXN1α-NLGN1 interaction of T737M and D772G mutants. (iii) In silico 3D structural modeling indicated that T737M and D772G mutations could destabilize the rod-shaped structure of LNS2-LNS5 domains, and D772G and R856W could disturb N-glycan conformations for the transport signal.


    </sec>
    <sec>
    <title>Conclusions</title>
    The combined data suggest that missense variants in <italic>NRXN1</italic> could be associated with phenotypes of neurodevelopmental disorders beyond the diagnosis of ASD and/or SCZ.


    </sec>

    DOI: 10.1186/s11689-020-09325-2

    その他リンク: http://link.springer.com/article/10.1186/s11689-020-09325-2/fulltext.html

  32. Rare single-nucleotide DAB1 variants and their contribution to Schizophrenia and autism spectrum disorder susceptibility 国際誌

    Yoshihiro Nawa, Hiroki Kimura, Daisuke Mori, Hidekazu Kato, Miho Toyama, Sho Furuta, Yanjie Yu, Kanako Ishizuka, Itaru Kushima, Branko Aleksic, Yuko Arioka, Mako Morikawa, Takashi Okada, Toshiya Inada, Kozo Kaibuchi, Masashi Ikeda, Nakao Iwata, Michio Suzuki, Yuko Okahisa, Jun Egawa, Toshiyuki Someya, Fumichika Nishimura, Tsukasa Sasaki, Norio Ozaki

    Human Genome Variation   7 巻 ( 1 ) 頁: 37 - 37   2020年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media {LLC}  

    Disabled 1 (DAB1) is an intracellular adaptor protein in the Reelin signaling pathway and plays an essential role in correct neuronal migration and layer formation in the developing brain. DAB1 has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in genetic, animal, and postmortem studies. Recently, increasing attention has been given to rare single-nucleotide variants (SNVs) found by deep sequencing of candidate genes. In this study, we performed exon-targeted resequencing of DAB1 in 370 SCZ and 192 ASD patients using next-generation sequencing technology to identify rare SNVs with a minor allele frequency <1%. We detected two rare missense mutations (G382C, V129I) and then performed a genetic association study in a sample comprising 1763 SCZ, 380 ASD, and 2190 healthy control subjects. Although no statistically significant association with the detected mutations was observed for either SCZ or ASD, G382C was found only in the case group, and in silico analyses and in vitro functional assays suggested that G382C alters the function of the DAB1 protein. The rare variants of DAB1 found in the present study should be studied further to elucidate their potential functional relevance to the pathophysiology of SCZ and ASD.

    DOI: 10.1038/s41439-020-00125-7

    PubMed

  33. Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder

    Hidekazu Kato, Itaru Kushima, Daisuke Mori, Akira Yoshimi, Branko Aleksic, Yoshihiro Nawa, Miho Toyama, Sho Furuta, Yanjie Yu, Kanako Ishizuka, Hiroki Kimura, Yuko Arioka, Keita Tsujimura, Mako Morikawa, Takashi Okada, Toshiya Inada, Masahiro Nakatochi, Keiko Shinjo, Yutaka Kondo, Kozo Kaibuchi, Yasuko Funabiki, Ryo Kimura, Toshimitsu Suzuki, Kazuhiro Yamakawa, Masashi Ikeda, Nakao Iwata, Tsutomu Takahashi, Michio Suzuki, Yuko Okahisa, Manabu Takaki, Jun Egawa, Toshiyuki Someya, Norio Ozaki

    Translational Psychiatry   10 巻 ( 1 )   2020年12月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media LLC  

    <title>Abstract</title>Dysregulation of epigenetic processes involving histone methylation induces neurodevelopmental impairments and has been implicated in schizophrenia (SCZ) and autism spectrum disorder (ASD). Variants in the gene encoding lysine demethylase 4C (<italic>KDM4C</italic>) have been suggested to confer a risk for such disorders. However, rare genetic variants in <italic>KDM4C</italic> have not been fully evaluated, and the functional impact of the variants has not been studied using patient-derived cells. In this study, we conducted copy number variant (CNV) analysis in a Japanese sample set (2605 SCZ and 1141 ASD cases, and 2310 controls). We found evidence for significant associations between CNVs in <italic>KDM4C</italic> and SCZ (<italic>p</italic> = 0.003) and ASD (<italic>p</italic> = 0.04). We also observed a significant association between deletions in <italic>KDM4C</italic> and SCZ (corrected <italic>p</italic> = 0.04). Next, to explore the contribution of single nucleotide variants in <italic>KDM4C</italic>, we sequenced the coding exons in a second sample set (370 SCZ and 192 ASD cases) and detected 18 rare missense variants, including p.D160N within the JmjC domain of KDM4C. We, then, performed association analysis for p.D160N in a third sample set (1751 SCZ and 377 ASD cases, and 2276 controls), but did not find a statistical association with these disorders. Immunoblotting analysis using lymphoblastoid cell lines from a case with <italic>KDM4C</italic> deletion revealed reduced KDM4C protein expression and altered histone methylation patterns. In conclusion, this study strengthens the evidence for associations between <italic>KDM4C</italic> CNVs and these two disorders and for their potential functional effect on histone methylation patterns.

    DOI: 10.1038/s41398-020-01107-7

    その他リンク: http://www.nature.com/articles/s41398-020-01107-7

  34. Identifying the brain's connector hubs at the voxel level using functional connectivity overlap ratio 国際誌

    Epifanio Bagarinao, Hirohisa Watanabe, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Kazuya Kawabata, Reiko Ohdake, Michihito Masuda, Aya Ogura, Toshiyasu Kato, Shuji Koyama, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Norio Ozaki, Gen Sobue

    NeuroImage   222 巻   頁: 117241 - 117241   2020年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Elsevier {BV}  

    Neuroimaging studies have shown that the brain is functionally organized into several large-scale brain networks. Within these networks are regions that are widely connected to several other regions within and/or outside the network. Regions that connect to several other networks, known as connector hubs, are believed to be crucial for information transfer and between-network communication within the brain. To identify regions with high between-network connectivity at the voxel level, we introduced a novel metric called functional connectivity overlap ratio (FCOR), which quantifies the spatial extent of a region's connection to a given network. Using resting state functional magnetic resonance imaging data, FCOR maps were generated for several well-known large-scale resting state networks (RSNs) and used to examine the relevant associations among different RSNs, identify connector hub regions in the cerebral cortex, and elucidate the hierarchical functional organization of the brain. Constructed FCOR maps revealed a strong association among the core neurocognitive networks (default mode, salience, and executive control) as well as among primary processing networks (sensorimotor, auditory, and visual). Prominent connector hubs were identified in the bilateral middle frontal gyrus, posterior cingulate, lateral parietal, middle temporal, dorsal anterior cingulate, and anterior insula, among others, regions mostly associated with the core neurocognitive networks. Finally, clustering the whole brain using FCOR features yielded a topological organization that arranges brain regions into a hierarchy of information processing systems with the primary processing systems at one end and the heteromodal systems comprising connector hubs at the other end.

    DOI: 10.1016/j.neuroimage.2020.117241

    PubMed

  35. Aging Impacts the Overall Connectivity Strength of Regions Critical for Information Transfer Among Brain Networks

    Epifanio Bagarinao, Hirohisa Watanabe, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Kazuya Kawabata, Noritaka Yoneyama, Reiko Ohdake, Kazunori Imai, Michihito Masuda, Takamasa Yokoi, Aya Ogura, Toshiaki Taoka, Shuji Koyama, Hiroki C. Tanabe, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Norio Ozaki, Gen Sobue

    Frontiers in Aging Neuroscience   12 巻   2020年10月

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    掲載種別:研究論文(学術雑誌)   出版者・発行元:Frontiers Media SA  

    DOI: 10.3389/fnagi.2020.592469

  36. Effects of Head Motion on the Evaluation of Age-related Brain Network Changes Using Resting State Functional MRI.

    Sanae Kato, Epifanio Bagarinao, Haruo Isoda, Shuji Koyama, Hirohisa Watanabe, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Masahisa Katsuno, Minoru Hoshiyama, Shinji Naganawa, Norio Ozaki, Gen Sobue

    Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine   20 巻 ( 4 ) 頁: 338 - 346   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    PURPOSE: The estimation of functional connectivity (FC) measures using resting state functional MRI (fMRI) is often affected by head motion during functional imaging scans. Head motion is more common in the elderly than in young participants and could therefore affect the evaluation of age-related changes in brain networks. Thus, this study aimed to investigate the influence of head motion in FC estimation when evaluating age-related changes in brain networks. METHODS: This study involved 132 healthy volunteers divided into 3 groups: elderly participants with high motion (OldHM, mean age (±SD) = 69.6 (±5.31), N = 44), elderly participants with low motion (OldLM, mean age (±SD) = 68.7 (±4.59), N = 43), and young adult participants with low motion (YugLM, mean age (±SD) = 27.6 (±5.26), N = 45). Head motion was quantified using the mean of the framewise displacement of resting state fMRI data. After preprocessing all resting state fMRI datasets, several resting state networks (RSNs) were extracted using independent component analysis (ICA). In addition, several network metrics were also calculated using network analysis. These FC measures were then compared among the 3 groups. RESULTS: In ICA, the number of voxels with significant differences in RSNs was higher in YugLM vs. OldLM comparison than in YugLM vs. OldHM. In network analysis, all network metrics showed significant (P < 0.05) differences in comparisons involving low vs. high motion groups (OldHM vs. OldLM and OldHM vs. YugLM). However, there was no significant (P > 0.05) difference in the comparison involving the low motion groups (OldLM vs. YugLM). CONCLUSION: Our findings showed that head motion during functional imaging could significantly affect the evaluation of age-related brain network changes using resting state fMRI data.

    DOI: 10.2463/mrms.mp.2020-0081

    PubMed

  37. Generation and analysis of novel Reln-deleted mouse model corresponding to exonic Reln deletion in schizophrenia. 査読有り 国際誌

    Masahito Sawahata, Daisuke Mori, Yuko Arioka, Hisako Kubo, Itaru Kushima, Kanako Kitagawa, Akira Sobue, Emiko Shishido, Mariko Sekiguchi, Akiko Kodama, Ryosuke Ikeda, Branko Aleksic, Hiroki Kimura, Kanako Ishizuka, Taku Nagai, Kozo Kaibuchi, Toshitaka Nabeshima, Kiyofumi Yamada, Norio Ozaki

    Psychiatry and clinical neurosciences     2020年2月

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    担当区分:責任著者   記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIMS: A Japanese individual with schizophrenia harboring a novel exonic deletion in RELN was recently identified by genome-wide copy-number variation analysis. Thus, the present study aimed to generate and analyze a model mouse to clarify whether RELN deficiency is associated with the pathogenesis of schizophrenia. METHODS: A mouse line with a novel RELN exonic deletion (Reln-del) was established using the CRISPR/Cas9 method to elucidate the underlying molecular mechanism. Subsequently, general behavioral tests and histopathological examinations of the model mice were conducted and phenotypic analysis of the cerebellar granule cell migration was performed. RESULTS: The phenotype of homozygous Reln-del mice was similar to that of reeler mice with cerebellar atrophy, dysplasia of the cerebral layers, and abrogated protein levels of cerebral reelin. The expression of reelin in heterozygous Reln-del mice was approximately half of that in wild-type mice. Conversely, behavioral analyses in heterozygous Reln-del mice without cerebellar atrophy or dysplasia showed abnormal social novelty in the three-chamber social interaction test. In vitro reaggregation formation and neuronal migration were severely altered in the cerebellar cultures of homozygous Reln-del mice. CONCLUSIONS: The present results in novel Reln-del mice modeled after our patient with a novel exonic deletion in RELN are expected to contribute to the development of reelin-based therapies for schizophrenia. This article is protected by copyright. All rights reserved.

    DOI: 10.1111/pcn.12993

    PubMed

  38. Comprehensive analysis of a novel mouse model of the 22q11.2 deletion syndrome: a model with the most common 3.0-Mb deletion at the human 22q11.2 locus. 査読有り 国際誌

    Ryo Saito, Michinori Koebis, Taku Nagai, Kimiko Shimizu, Jingzhu Liao, Bolati Wulaer, Yuki Sugaya, Kenichiro Nagahama, Naofumi Uesaka, Itaru Kushima, Daisuke Mori, Kazuaki Maruyama, Kazuki Nakao, Hiroki Kurihara, Kiyofumi Yamada, Masanobu Kano, Yoshitaka Fukada, Norio Ozaki, Atsu Aiba

    Translational psychiatry   10 巻 ( 1 ) 頁: 35 - 35   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The 22q11.2 deletion syndrome (22q11.2DS) is associated with an increased risk for psychiatric disorders. Although most of the 22q11.2DS patients have a 3.0-Mb deletion, existing mouse models only mimic a minor mutation of 22q11.2DS, a 1.5-Mb deletion. The role of the genes existing outside the 1.5-Mb deletion in psychiatric symptoms of 22q11.2DS is unclear. In this study, we generated a mouse model that reproduced the 3.0-Mb deletion of the 22q11.2DS (Del(3.0 Mb)/ +) using the CRISPR/Cas9 system. Ethological and physiological phenotypes of adult male mutants were comprehensively evaluated by visual-evoked potentials, circadian behavioral rhythm, and a series of behavioral tests, such as measurement of locomotor activity, prepulse inhibition, fear-conditioning memory, and visual discrimination learning. As a result, Del(3.0 Mb)/ + mice showed reduction of auditory prepulse inhibition and attenuated cue-dependent fear memory, which is consistent with the phenotypes of existing 22q11.2DS models. In addition, Del(3.0 Mb)/ + mice displayed an impaired early visual processing that is commonly seen in patients with schizophrenia. Meanwhile, unlike the existing models, Del(3.0 Mb)/ + mice exhibited hypoactivity over several behavioral tests, possibly reflecting the fatigability of 22q11.2DS patients. Lastly, Del(3.0 Mb)/ + mice displayed a faster adaptation to experimental jet lag as compared with wild-type mice. Our results support the validity of Del(3.0 Mb)/ + mice as a schizophrenia animal model and suggest that our mouse model is a useful resource to understand pathogenic mechanisms of schizophrenia and other psychiatric disorders associated with 22q11.2DS.

    DOI: 10.1038/s41398-020-0723-z

    PubMed

  39. Cell body shape and directional movement stability in human-induced pluripotent stem cell-derived dopaminergic neurons 国際誌

    Arioka, Y., Shishido, E., Kushima, I., Mori, D., Ozaki, N.

    Scientific Reports   10 巻 ( 1 ) 頁: 5820 - 5820   2020年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Springer Science and Business Media {LLC}  

    Neuronal migration is necessary in the process of the formation of brain architecture. Recently, we demonstrated that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons exhibit directional migration in vitro. However, it remains unclear how the cell shape is involved in their migration. In this study, we performed live imaging analyses using human iPSC-derived dopaminergic neurons. Our automated method, which can automatically identify the cell body shape and the cell position at specific time points, revealed that healthy iPSC-derived dopaminergic neurons migrate according to their shape. This migration behavior was out of accord in neurons derived from iPSCs carrying an RELN deletion. Our findings provide a novel theory that cell body orientation is related to the stability of movement direction for human dopaminergic neurons, under the regulation of RELN.

    DOI: 10.1038/s41598-020-62598-4

    Scopus

    PubMed

  40. Characterization of a schizophrenia patient with a rare RELN deletion by combining genomic and patient-derived cell analyses. 査読有り 国際誌

    Yuko Arioka, Akihiro Hirata, Itaru Kushima, Branko Aleksic, Daisuke Mori, Norio Ozaki

    Schizophrenia research     2019年12月

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    記述言語:英語  

    Genetic studies have identified rare RELN variants as risk factors for psychiatric disorders. However, additional genetic factors appear to be necessary for disease onset. Detailed genetic information and the use of patient-derived neuronal cells may thus enable to discover these disease-related additional factors. Here, we performed whole-genome sequencing of a schizophrenia patient with a rare RELN deletion and his healthy mother, and examined the phenotypes of 3D-cultured neuronal cells derived from induced pluripotent stem cells of this patient. Our results revealed that, along with the RELN deletion, neuronal death was promoted in this patient; thus, neuronal death may be a vulnerable factor for schizophrenia.

    DOI: 10.1016/j.schres.2019.10.038

    PubMed

  41. In Vitro Modeling of the Bipolar Disorder and Schizophrenia Using Patient-Derived Induced Pluripotent Stem Cells with Copy Number Variations of PCDH15 and RELN 査読有り

    Takaya Ishii, Mitsuru Ishikawa, Koki Fujimori, Takuji Maeda, Itaru Kushima, Yuko Arioka, Daisuke Mori, Yuhki Nakatake, Bun Yamagata, Shintaro Nio, Takahiro A. Kato, Nan Yang, Marius Wernig, Shigenobu Kanba, Masaru Mimura, Norio Ozaki, Hideyuki Okano

    eneuro     頁: ENEURO.0403   2019年9月

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    出版者・発行元:Society for Neuroscience  

    DOI: 10.1523/ENEURO.0403-18.2019

  42. Reorganization of brain networks and its association with general cognitive performance over the adult lifespan. 査読有り 国際誌

    Epifanio Bagarinao, Hirohisa Watanabe, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Kazuya Kawabata, Noritaka Yoneyama, Reiko Ohdake, Kazunori Imai, Michihito Masuda, Takamasa Yokoi, Aya Ogura, Toshiaki Taoka, Shuji Koyama, Hiroki C Tanabe, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Norio Ozaki, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Gen Sobue

    Scientific reports   9 巻 ( 1 ) 頁: 11352 - 11352   2019年8月

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    記述言語:英語   出版者・発行元:Springer Science and Business Media {LLC}  

    Healthy aging is associated with structural and functional changes in the brain even in individuals who are free of neurodegenerative diseases. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of participants, we examined cross sectional changes in the functional organization of several large-scale brain networks over the adult lifespan and its potential association with general cognitive performance. Converging results from multiple analyses at the voxel, node, and network levels showed widespread reorganization of functional brain networks with increasing age. Specifically, the primary processing (visual and sensorimotor) and visuospatial (dorsal attention) networks showed diminished network integrity, while the so-called core neurocognitive (executive control, salience, and default mode) and basal ganglia networks exhibited relatively preserved between-network connections. The visuospatial and precuneus networks also showed significantly more widespread increased connectivity with other networks. Graph analysis suggested that this reorganization progressed towards a more integrated network topology. General cognitive performance, assessed by Addenbrooke's Cognitive Examination-Revised total score, was positively correlated with between-network connectivity among the core neurocognitive and basal ganglia networks and the integrity of the primary processing and visuospatial networks. Mediation analyses further indicated that the observed association between aging and relative decline in cognitive performance could be mediated by changes in relevant functional connectivity measures. Overall, these findings provided further evidence supporting widespread age-related brain network reorganization and its potential association with general cognitive performance during healthy aging.

    DOI: 10.1038/s41598-019-47922-x

    PubMed

  43. Quantitative facial expression analysis revealed the efficacy and time course of oxytocin in autism.

    Owada K, Okada T, Munesue T, Kuroda M, Fujioka T, Uno Y, Matsumoto K, Kuwabara H, Mori D, Okamoto Y, Yoshimura Y, Kawakubo Y, Arioka Y, Kojima M, Yuhi T, Yassin W, Kushima I, Benner S, Ogawa N, Kawano N, Eriguchi Y, Uemura Y, Yamamoto M, Kano Y, Kasai K, Higashida H, Ozaki N, Kosaka H, Yamasue H

    Brain : a journal of neurology     2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1093/brain/awz126

    PubMed

  44. Author Correction: Proteomic analysis of lymphoblastoid cell lines from schizophrenic patients (Translational Psychiatry, (2019), 9, 1, (126), 10.1038/s41398-019-0461-2) 査読有り 国際誌

    Yoshimi, A., Yamada, S., Kunimoto, S., Aleksic, B., Hirakawa, A., Ohashi, M., Matsumoto, Y., Hada, K., Itoh, N., Arioka, Y., Kimura, H., Kushima, I., Nakamura, Y., Shiino, T., Mori, D., Tanaka, S., Hamada, S., Noda, Y., Nagai, T., Yamada, K., Ozaki, N.

    Translational Psychiatry   9 巻 ( 1 ) 頁: 146 - 146   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    The original Article required a few updates; one co-author name, which was given as Hiroki Kiumura, has been updated to Hiroki Kimura. Furthermore, supplementary information has been updated, and grant numbers have been added. These updates have been made to both the PDF and HTML versions of this Article.

    DOI: 10.1038/s41398-019-0479-5

    Scopus

    PubMed

  45. Assessment of a glyoxalase I frameshift variant, p.P122fs, in Japanese patients with schizophrenia. 査読有り 国際誌

    Kanako Ishizuka, Hiroki Kimura, Itaru Kushima, Toshiya Inada, Yuko Okahisa, Masashi Ikeda, Nakao Iwata, Daisuke Mori, Branko Aleksic, Norio Ozaki

    Psychiatric genetics   28 巻 ( 5 ) 頁: 90 - 93   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Enhanced carbonyl stress has been observed in a subgroup of patients with schizophrenia. Glyoxalase I, which is encoded by GLO1, is an enzyme that protects against carbonyl stress. In this study, we focused on the association between rare genetic variants of GLO1 and schizophrenia. First, we identified one heterozygous frameshift variant, p.P122fs, in 370 Japanese schizophrenia cases with allele frequencies of up to 1% by exon-targeted mutation screening of GLO1. We then performed an association analysis on 1282 cases and 1764 controls with this variant. The variant was found in three cases and eight controls. There was no statistically significant association between p.P122fs in GLO1 and schizophrenia (P=0.25). This frameshift variant in GLO1 might occur at near-polymorphic frequencies in the Japanese population, although further investigations using larger samples and biological analyses are needed to exclude the possibility of a low-penetrance genetic risk associated with this variant.

    DOI: 10.1097/YPG.0000000000000204

    PubMed

  46. Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights. 査読有り 国際誌

    Itaru Kushima, Branko Aleksic, Masahiro Nakatochi, Teppei Shimamura, Takashi Okada, Yota Uno, Mako Morikawa, Kanako Ishizuka, Tomoko Shiino, Hiroki Kimura, Yuko Arioka, Akira Yoshimi, Yuto Takasaki, Yanjie Yu, Yukako Nakamura, Maeri Yamamoto, Tetsuya Iidaka, Shuji Iritani, Toshiya Inada, Nanayo Ogawa, Emiko Shishido, Youta Torii, Naoko Kawano, Yutaka Omura, Toru Yoshikawa, Tokio Uchiyama, Toshimichi Yamamoto, Masashi Ikeda, Ryota Hashimoto, Hidenaga Yamamori, Yuka Yasuda, Toshiyuki Someya, Yuichiro Watanabe, Jun Egawa, Ayako Nunokawa, Masanari Itokawa, Makoto Arai, Mitsuhiro Miyashita, Akiko Kobori, Michio Suzuki, Tsutomu Takahashi, Masahide Usami, Masaki Kodaira, Kyota Watanabe, Tsukasa Sasaki, Hitoshi Kuwabara, Mamoru Tochigi, Fumichika Nishimura, Hidenori Yamasue, Yosuke Eriguchi, Seico Benner, Masaki Kojima, Walid Yassin, Toshio Munesue, Shigeru Yokoyama, Ryo Kimura, Yasuko Funabiki, Hirotaka Kosaka, Makoto Ishitobi, Tetsuro Ohmori, Shusuke Numata, Takeo Yoshikawa, Tomoko Toyota, Kazuhiro Yamakawa, Toshimitsu Suzuki, Yushi Inoue, Kentaro Nakaoka, Yu-Ichi Goto, Masumi Inagaki, Naoki Hashimoto, Ichiro Kusumi, Shuraku Son, Toshiya Murai, Tempei Ikegame, Naohiro Okada, Kiyoto Kasai, Shohko Kunimoto, Daisuke Mori, Nakao Iwata, Norio Ozaki

    Cell reports   24 巻 ( 11 ) 頁: 2838 - 2856   2018年9月

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    記述言語:英語  

    Compelling evidence in Caucasian populations suggests a role for copy-number variations (CNVs) in autism spectrum disorder (ASD) and schizophrenia (SCZ). We analyzed 1,108 ASD cases, 2,458 SCZ cases, and 2,095 controls in a Japanese population and confirmed an increased burden of rare exonic CNVs in both disorders. Clinically significant (or pathogenic) CNVs, including those at 29 loci common to both disorders, were found in about 8% of ASD and SCZ cases, which was significantly higher than in controls. Phenotypic analysis revealed an association between clinically significant CNVs and intellectual disability. Gene set analysis showed significant overlap of biological pathways in both disorders including oxidative stress response, lipid metabolism/modification, and genomic integrity. Finally, based on bioinformatics analysis, we identified multiple disease-relevant genes in eight well-known ASD/SCZ-associated CNV loci (e.g., 22q11.2, 3q29). Our findings suggest an etiological overlap of ASD and SCZ and provide biological insights into these disorders.

    DOI: 10.1016/j.celrep.2018.08.022

    PubMed

  47. 統合失調症に強い関連を示した稀な遺伝子変異に基づく精神疾患の分子病態解明

    木村 大樹, 藤田 幸, 川端 猛, 森 大輔, 岩山 佳美, 岡久 祐子, 池田 匡志, 岩田 仲生, 吉川 武男, 山下 俊英, 中村 春木, 尾崎 紀夫

    先進医薬研究振興財団研究成果報告集   2017年度 巻   頁: 80 - 81   2018年3月

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    記述言語:日本語   出版者・発行元:(公財)先進医薬研究振興財団  

  48. Genetic and animal model analyses reveal the pathogenic role of a novel deletion of RELN in schizophrenia 査読有り

    Sobue Akira, Kushima Itaru, Nagai Taku, Shan Wei, Kohno Takao, Aleksic Branko, Aoyama Yuki, Mori Daisuke, Arioka Yuko, Kawano Naoko

    Scientific reports   8 巻 ( 1 ) 頁: 13046   2018年

  49. Three lines of induced pluripotent stem cells derived from a 15q11. 2-q13. 1 duplication syndrome patient 査読有り

    Arioka Yuko, Kushima Itaru, Mori Daisuke, Ozaki Norio

    Stem Cell Research     2018年

  50. MUTATION SCREENING OF THE PCDH15 GENE IN PATIENTS SUFFERING FROM AUTISM SPECTRUM DISORDERS AND SCHIZOPHRENIA 査読有り

    Kanako Ishizuka, Chenyao Wang, Hiroki Kimura, Jingrui Xing, Itaru Kushima, Yuko Arioka, Akira Yoshimi, Yukako Nakamura, Tomoko Oya-Ito, Yuto Takasaki, Yota Uno, Takashi Okada, Daisuke Mori, Branko Aleksic, Norio Ozaki

    EUROPEAN NEUROPSYCHOPHARMACOLOGY   27 巻   頁: S162 - S163   2017年10月

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    記述言語:英語   掲載種別:研究論文(国際会議プロシーディングス)  

    Web of Science

  51. Rare genetic variants in CX3CR1 and their contribution to the increased risk of schizophrenia and autism spectrum disorders 査読有り

    K. Ishizuka, Y. Fujita, T. Kawabata, H. Kimura, Y. Iwayama, T. Inada, Y. Okahisa, J. Egawa, M. Usami, I. Kushima, Y. Uno, T. Okada, M. Ikeda, B. Aleksic, D. Mori, To Someya, T. Yoshikawa, N. Iwata, H. Nakamura, T. Yamashita, N. Ozaki

    TRANSLATIONAL PSYCHIATRY   7 巻 ( 8 ) 頁: e1184   2017年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    CX3CR1, a G protein-coupled receptor solely expressed by microglia in the brain, has been repeatedly reported to be associated with neurodevelopmental disorders including schizophrenia (SCZ) and autism spectrum disorders (ASD) in transcriptomic and animal studies but not in genetic studies. To address the impacts of variants in CX3CR1 on neurodevelopmental disorders, we conducted coding exon-targeted resequencing of CX3CR1 in 370 Japanese SCZ and 192 ASD patients using next-generation sequencing technology, followed by a genetic association study in a sample comprising 7054 unrelated individuals (2653 SCZ, 574 ASD and 3827 controls). We then performed in silico three-dimensional (3D) structural modeling and in vivo disruption of Akt phosphorylation to determine the impact of the detected variant on CX3CR1-dependent signal transduction. We detected a statistically significant association between the variant Ala55Thr in CX3CR1 with SCZ and ASD phenotypes (odds ratio = 8.3, P = 0.020). A 3D structural model indicated that Ala55Thr could destabilize the conformation of the CX3CR1 helix 8 and affect its interaction with a heterotrimeric G protein. In vitro functional analysis showed that the CX3CR1-Ala55Thr mutation inhibited cell signaling induced by fractalkine, the ligand for CX3CR1. The combined data suggested that the variant Ala55Thr in CX3CR1 might result in the disruption of CX3CR1 signaling. Our results strengthen the association between microglia-specific genes and neurodevelopmental disorders.

    DOI: 10.1038/tp.2017.173

    Web of Science

  52. High-resolution copy number variation analysis of schizophrenia in Japan 査読有り

    I. Kushima, B. Aleksic, M. Nakatochi, T. Shimamura, T. Shiino, A. Yoshimi, H. Kimura, Y. Takasaki, C. Wang, J. Xing, K. Ishizuka, T. Oya-Ito, Y. Nakamura, Y. Arioka, T. Maeda, M. Yamamoto, M. Yoshida, H. Noma, S. Hamada, M. Morikawa, Y. Uno, T. Okada, T. Iidaka, S. Iritani, T. Yamamoto, M. Miyashita, A. Kobori, M. Arai, M. Itokawa, M-C Cheng, Y-A Chuang, C-H Chen, M. Suzuki, T. Takahashi, R. Hashimoto, H. Yamamori, Y. Yasuda, Y. Watanabe, A. Nunokawa, T. Someya, M. Ikeda, T. Toyota, T. Yoshikawa, S. Numata, T. Ohmori, S. Kunimoto, D. Mori, N. Iwata, N. Ozaki

    MOLECULAR PSYCHIATRY   22 巻 ( 3 ) 頁: 430 - 440   2017年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (&lt; 100 kb). Clinically significant CNVs were significantly more frequent in cases than in controls (odds ratio = 3.04, P = 9.3 x 10 (-9), 9.0% of cases). We confirmed a significant association of X-chromosome aneuploidies with SCZ and identified 11 de novo CNVs (e. g., MBD5 deletion) in cases. In patients with clinically significant CNVs, 41.7% had a history of congenital/developmental phenotypes, and the rate of treatment resistance was significantly higher (odds ratio = 2.79, P = 0.0036). We found more severe clinical manifestations in patients with two clinically significant CNVs. Gene set analysis replicated previous findings (e. g., synapse, calcium signaling) and identified novel biological pathways including oxidative stress response, genomic integrity, kinase and small GTPase signaling. Furthermore, involvement of multiple SCZ candidate genes and biological pathways in the pathogenesis of SCZ was suggested in established SCZ-associated CNV loci. Our study shows the high genetic heterogeneity of SCZ and its clinical features and raises the possibility that genomic instability is involved in its pathogenesis, which may be related to the increased burden of de novo CNVs and variable expressivity of CNVs.

    DOI: 10.1038/mp.2016.88

    Web of Science

    その他リンク: http://orcid.org/0000-0002-9072-2546

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MISC 12

  1. ARHGAP10遺伝子変異と統合失調症発症の関連(Japanese)

    Daisuke Mori  

    精神科臨床Legato   2021年4月

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    記述言語:日本語  

  2. Changes in white matter fiber density and morphology across the adult lifespan: A cross-sectional fixel-based analysis. 国際誌

    Shao Wei Choy, Epifanio Bagarinao, Hirohisa Watanabe, Eric Tatt Wei Ho, Satoshi Maesawa, Daisuke Mori, Kazuhiro Hara, Kazuya Kawabata, Noritaka Yoneyama, Reiko Ohdake, Kazunori Imai, Michihito Masuda, Takamasa Yokoi, Aya Ogura, Toshiaki Taoka, Shuji Koyama, Hiroki C Tanabe, Masahisa Katsuno, Toshihiko Wakabayashi, Masafumi Kuzuya, Minoru Hoshiyama, Haruo Isoda, Shinji Naganawa, Norio Ozaki, Gen Sobue  

    Human brain mapping   2020年4月

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    記述言語:英語  

    White matter (WM) fiber bundles change dynamically with age. These changes could be driven by alterations in axonal diameter, axonal density, and myelin content. In this study, we applied a novel fixel-based analysis (FBA) framework to examine these changes throughout the adult lifespan. Using diffusion-weighted images from a cohort of 293 healthy volunteers (89 males/204 females) from ages 21 to 86 years old, we performed FBA to analyze age-related changes in microscopic fiber density (FD) and macroscopic fiber morphology (fiber cross section [FC]). Our results showed significant and widespread age-related alterations in FD and FC across the whole brain. Interestingly, some fiber bundles such as the anterior thalamic radiation, corpus callosum, and superior longitudinal fasciculus only showed significant negative relationship with age in FD values, but not in FC. On the other hand, some segments of the cerebello-thalamo-cortical pathway only showed significant negative relationship with age in FC, but not in FD. Analysis at the tract-level also showed that major fiber tract groups predominantly distributed in the frontal lobe (cingulum, forceps minor) exhibited greater vulnerability to the aging process than the others. Differences in FC and the combined measure of FD and cross section values observed between sexes were mostly driven by differences in brain sizes although male participants tended to exhibit steeper negative linear relationship with age in FD as compared to female participants. Overall, these findings provide further insights into the structural changes the brain's WM undergoes due to the aging process.

    DOI: 10.1002/hbm.25008

    PubMed

  3. Psychiatric-disorder-related behavioral phenotypes and cortical hyperactivity in a mouse model of 3q29 deletion syndrome. 国際誌

    Masayuki Baba, Kazumasa Yokoyama, Kaoru Seiriki, Yuichiro Naka, Kensuke Matsumura, Momoka Kondo, Kana Yamamoto, Misuzu Hayashida, Atsushi Kasai, Yukio Ago, Kazuki Nagayasu, Atsuko Hayata-Takano, Akinori Takahashi, Shun Yamaguchi, Daisuke Mori, Norio Ozaki, Tadashi Yamamoto, Kazuhiro Takuma, Ryota Hashimoto, Hitoshi Hashimoto, Takanobu Nakazawa  

    Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology44 巻 ( 12 ) 頁: 2125 - 2135   2019年11月

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    記述言語:英語  

    3q29 microdeletion, a rare recurrent copy number variant (CNV), greatly confers an increased risk of psychiatric disorders, such as schizophrenia and autism spectrum disorder (ASD), as well as intellectual disability. However, disease-relevant cellular phenotypes of 3q29 deletion syndrome remain to be identified. To reveal the molecular and cellular etiology of 3q29 deletion syndrome, we generated a mouse model of human 3q29 deletion syndrome by chromosome engineering, which achieved construct validity. 3q29 deletion (Df/+) mice showed reduced body weight and brain volume and, more importantly, impaired social interaction and prepulse inhibition. Importantly, the schizophrenia-related impaired prepulse inhibition was reversed by administration of antipsychotics. These findings are reminiscent of the growth defects and neuropsychiatric behavioral phenotypes in patients with 3q29 deletion syndrome and exemplify that the mouse model achieves some part of face validity and predictive validity. Unbiased whole-brain imaging revealed that neuronal hyperactivation after a behavioral task was strikingly exaggerated in a restricted region of the cortex of Df/+ mice. We further elucidated the cellular phenotypes of neuronal hyperactivation and the reduction of parvalbumin expression in the cortex of Df/+ mice. Thus, the 3q29 mouse model provides invaluable insight into the disease-causative molecular and cellular pathology of psychiatric disorders.

    DOI: 10.1038/s41386-019-0441-5

    PubMed

  4. 精神疾患ゲノム解析に基づくシナプス病態研究の新知見(Japanese)

    Daisuke Mori  

    月刊細胞   2018年12月

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    記述言語:日本語  

  5. 統合失調症に強い関連を示した稀な遺伝子変異に基づく精神疾患の分子病態解明

    木村 大樹, 藤田 幸, 川端 猛, 森 大輔, 岩山 佳美, 岡久 祐子, 池田 匡志, 岩田 仲生, 吉川 武男, 山下 俊英, 中村 春木, 尾崎 紀夫  

    先進医薬研究振興財団研究成果報告集2017年度 巻   頁: 80 - 81   2018年3月

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    記述言語:日本語   出版者・発行元:(公財)先進医薬研究振興財団  

  6. RELN遺伝子の統合失調症関連新規欠失のマウス皮質における組織学的解析

    KITAGAWA Kanako, SAWAHATA Masahito, MORI Daisuke, MORI Daisuke, SAGARA Atsunobu, NAGAI Taku, SOBUE Akira, TSUNEURA Yumi, TAKASE Saeko, OZAKI Norio, NABESHIMA Toshitaka, NABESHIMA Toshitaka, YAMADA Kiyofumi  

    次世代を担う若手医療薬科学シンポジウム抄録集12th 巻   2018年

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  7. IDENTIFICATION OF RARE DISRUPTIVE VARIANTS IN VOLTAGE-GATED CHANNEL GENES (CACNA1C, CACNA1D, CACNA1S, CACNA1I) IN JAPANESE SAMPLES OF SCHIZOPHRENIA AND AUTISM SPECTRUM DISORDER USING ION TORRENT PGM PLATFORM

    Chenyao Wang, Hiroki Kimura, Jingrui Xing, Kanoko Ishizuka, Itaru Kushima, Yuko Arioka, Akira Yoshimi, Yukako Nakamura, Yomoko Shiino, Yuko Oya, Yuto Takasaki, Branko Aleksic, Daisuke Mori, Norio Ozaki  

    EUROPEAN NEUROPSYCHOPHARMACOLOGY27 巻   頁: S341 - S342   2017年10月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:ELSEVIER SCIENCE BV  

    Web of Science

  8. MUTATION SCREENING OF THE PCDH15 GENE IN PATIENTS SUFFERING FROM AUTISM SPECTRUM DISORDERS AND SCHIZOPHRENIA

    Ishizuka Kanako, Wang Chenyao, Kimura Hiroki, Xing Jingrui, Kushima Itaru, Arioka Yuko, Yoshimi Akira, Nakamura Yukako, Oya-Ito Tomoko, Takasaki Yuto, Uno Yota, Okada Takashi, Mori Daisuke, Aleksic Branko, Ozaki Norio  

    EUROPEAN NEUROPSYCHOPHARMACOLOGY27 巻   頁: S162-S163   2017年10月

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    記述言語:英語   掲載種別:速報,短報,研究ノート等(学術雑誌)  

  9. 統合失調症発症に強い影響を及ぼす、頻度の低い稀な遺伝子変異を22q11.2欠失領域に存在するミエリン関連遺伝子のRTN4Rに同定した

    木村 大樹, 藤田 幸, 川端 猛, 石塚 佳奈子, Wang Chenyao, 岩山 佳美, 岡久 祐子, 久島 周, 宇野 洋太, 岡田 俊, 森川 真子, 森 大輔, 池田 匡志, 稲田 俊也, Aleksic Branko, 吉川 武男, 岩田 仲生, 中村 春木, 山下 俊英, 尾崎 紀夫  

    日本生物学的精神医学会・日本神経精神薬理学会合同年会プログラム・抄録集39回・47回 巻   頁: 190 - 190   2017年9月

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    記述言語:日本語   出版者・発行元:日本生物学的精神医学会・日本神経精神薬理学会  

  10. 本邦における統合失調症と自閉スペクトラム症に関連するGRIN2Bの遺伝子変異の探索

    高崎 悠登, 尾崎 紀夫, 小出 隆義, 王 晨堯, 木村 大樹, 久島 周, 石塚 佳奈子, 森 大輔, 池田 匡志, アレクシッチ・ブランコ, 岡田 俊, 江川 純, 桑原 斉, 染矢 俊幸, 吉川 武男, 岩田 仲生  

    精神神経学雑誌 ( 2017特別号 ) 頁: S626 - S626   2017年6月

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    記述言語:日本語   出版者・発行元:(公社)日本精神神経学会  

  11. 統合失調症発症に強い影響を及ぼす、頻度の低い稀な遺伝子変異を22q11.2欠失領域に存在するミエリン関連遺伝子のRTN4Rに同定した

    木村 大樹, 尾崎 紀夫, 藤田 幸, 川端 猛, 石塚 佳奈子, Wang Chenyao, 岩山 佳美, 岡久 祐子, 久島 周, 森川 真子, 宇野 洋太, 岡田 俊, 森 大輔, 池田 匡志, 稲田 俊也, Aleksic Branko, 吉川 武男, 岩田 仲生, 中村 春木, 山下 俊英  

    精神神経学雑誌 ( 2017特別号 ) 頁: S622 - S622   2017年6月

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    記述言語:日本語   出版者・発行元:(公社)日本精神神経学会  

  12. 本邦における統合失調症と自閉スペクトラム症に関連するGRIN2Bの遺伝子変異の探索

    高崎 悠登, 尾崎 紀夫, 小出 隆義, 王 晨堯, 木村 大樹, 久島 周, 石塚 佳奈子, 森 大輔, 池田 匡志, アレクシッチ・ブランコ, 岡田 俊, 江川 純, 桑原 斉, 染矢 俊幸, 吉川 武男, 岩田 仲生  

    精神神経学雑誌 ( 2017特別号 ) 頁: S626 - S626   2017年6月

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    記述言語:日本語   出版者・発行元:(公社)日本精神神経学会  

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科研費 6

  1. 精神疾患モデルマウスに特徴的な日周性活動量・体温変化

    研究課題/研究課題番号:22K07369  2022年4月 - 2025年3月

    日本学術振興会  科学研究費助成事業  基盤研究(C)

    森 大輔

  2. リーリン欠失統合失調症患者モデルマウスを用いた発症メカニズムの解明

    研究課題/研究課題番号:19K07384  2019年4月 - 2022年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    森 大輔

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    RELNに新規のエキソン欠失をもつ日本人の統合失調症患者をゲノムワイドコピー数多型解析により同定した。したがって、本研究ではReln欠失が統合失調症の病態に関与するかどうかを明らかにするため、マウスモデルを作製し、解析を行う事を目的とした。
    根底にある分子メカニズムを明らかにするため、CRISPR/Cas9法によってRELNの新規エキソン欠失をもつマウスライン(Reln‐del)を開発した。その後、マウスモデルの一般的な行動解析及び組織病理学的実験を行い、小脳顆粒細胞遊走の表現型解析を実施した。
    ホモ接合型のReln‐delマウスはreelerマウスと同様に小脳の萎縮、大脳層構造の形成異常、脳内reelinのタンパクレベルの消失といった表現型を示した。ヘテロ接合型のReln‐delマウスのreelin発現レベルは野生型の約半分程度であった。逆に小脳の萎縮や形成異常を認めないヘテロ接合型のReln‐delマウスは三部屋式社会性行動試験(Three-chambered social interaction test)において、異常なSocial noveltyを示した。In vitro 再集合形成や神経細胞遊走はホモ接合型のReln‐delマウスにおいて顕著に変化した。
    RELNの新規エキソン欠失をもつ我々の患者をモデルにした新規Reln‐delマウスの今回の結果は統合失調症のreelinに基づいた治療法開発に貢献する事が期待されるため、引き続き継続していく。

  3. リアルタイム機能的MRI-脳波同時測定装置を用いた時間的空間的脳内神経回路解析

    研究課題/研究課題番号:15K15338  2015年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業 挑戦的萌芽研究  挑戦的萌芽研究

    渡辺 宏久, 寳珠山 稔, 森 大輔, 田邊 宏樹, Bagarinao E., 祖父江 元, 伊藤 瑞規, 前澤 聡

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    本研究では、fMRIと脳波 (EEG) を組み合わせたEEG-fMRIを用い、fMRIの有する高い空間分解能を活かした解析に加え、脳波の有する高い時間分解能生を活かした解析を組み合わせて、ヒトの高次脳機能神経回路や精神症状をサブミリセカンドで観察出来るシステムを構築した。我々の解析方法を用いることで、作業記憶課題を用いた脳活動の観察では、認知課題中に1秒未満で連続的に変化する脳活動を観察可能であった。またてんかん活動を観察しつつ同定した焦点は、手術により確認したそれと良く一致していた。我々の開発した解析手法は、高い空間分解能で1秒未満の連続的な脳活動変化を捉えられる。

  4. 次世代の皮質下機能的脳外科手術の確立を目指したコネクトームマップの開発

    研究課題/研究課題番号:26462202  2014年4月 - 2017年3月

    日本学術振興会  科学研究費助成事業 基盤研究(C)  基盤研究(C)

    前澤 聡, 森 健策, 夏目 淳, バガリナオ エピファニオ, 森 大輔, 藤井 正純, 渡辺 宏久, 田邊 宏樹, 寳珠山 稔

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    脳ネットワーク画像解析の発展を背景に、安静時fMRIを基盤としDTIの解剖学的連絡とEEG-fMRIの電気生理学的連絡も重畳し、健常大規模データと比較する事でてんかんや脳腫瘍患者特有の“コネクトームマップ”を作成を目指した研究を進め、次の5つの成果を得た。(1)安静時fMRIで言語野、運動野が同定可能である事を示した。(2)新しい言語連絡であるfrontal aslant tractを報告した。(3) てんかんの安静時fMRIより異常結合同定の可能性を示した。(4)EEG-fMRIの新しいsubsecond解析を報告した。(5)術中ナビゲーションで関心領域からの結合性表示プログラムを作成した。

  5. Molecular biological analysis of BTEB2

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    資金種別:競争的資金

  6. 細胞分裂における中心体生化学的解析

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    資金種別:競争的資金

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担当経験のある科目 (本学以外) 4

  1. 生化学

    大阪市立大学)

  2. 基礎医学セミナー

    名古屋大学)

  3. Biochemistry

    Osaka-City University)

  4. Basic training course of medical research

    Nagoya Univercity)