基本情報
- 所属
- 自治医科大学 医学部組織学部門 准教授
- 学位
- 博士(医学)(京都大学)
- 研究者番号
- 30814587
- J-GLOBAL ID
- 201701018685256603
- researchmap会員ID
- B000281797
経歴
9-
2025年4月 - 現在
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2019年4月 - 2025年3月
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2017年10月 - 2022年9月
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2017年10月 - 2019年3月
学歴
2-
2004年4月 - 2014年3月
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2008年4月 - 2012年3月
論文
34-
Journal of Pharmacological Sciences 2025年2月
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Microscopy (Oxford, England) 2024年7月24日 査読有り招待有り筆頭著者最終著者責任著者Adapting to environmental changes and formulating behavioral strategies are central to the nervous system, with the prefrontal cortex being crucial. Chronic stress impacts this region, leading to disorders including major depression. This review discusses the roles for prefrontal cortex and the effects of stress, highlighting similarities and differences between human/primates and rodent brains. Notably, the rodent medial prefrontal cortex (mPFC) is analogous to the human subgenual anterior cingulate cortex (sgACC) in terms of emotional regulation, sharing similarities in cytoarchitecture and circuitry, while also performing cognitive functions similar to the human dorsolateral prefrontal cortex (DLPFC). It has been shown that chronic stress induces atrophic changes in the rodent mPFC, which mirrors the atrophy observed in the sgACC and DLPFC of depression patients. However, the precise alterations in neural circuitry due to chronic stress are yet to be fully unraveled. The use of advanced imaging techniques, particularly volume electron microscopy, is emphasized as critical for the detailed examination of synaptic changes, providing a deeper understanding of stress and depression at the molecular, cellular, and circuit levels. This approach offers invaluable insights into the alterations in neuronal circuits within the mPFC caused by chronic stress, significantly enriching our understanding of stress and depression pathologies.
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Journal of pharmacological sciences 154(4) 279-293 2024年4月 査読有り筆頭著者責任著者
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Scientific Reports 12(1) 2022年12月 査読有り
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Journal of proteome research 21(6) 1418-1427 2022年5月6日 査読有り
MISC
59-
日本薬理学会年会要旨集(Web) 97th 2023年
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日本薬理学会年会要旨集 95 1-SS-13 2022年Chronic social stress induces neuronal dysfunctions in the medial prefrontal cortex (mPFC) for emotional and cognitive disturbances. However, the subcellular mechanism remains elusive. Here we examined ultrastructural and multi-omics changes in the mPFC in a mouse model of social defeat stress. Acute stress induced dendritic membrane deformation with mitochondrial swelling in mPFC neurons, leading to dendritic atrophy after chronic stress. Synaptic, but not bulk tissue, proteomes in the mPFC differentiated naïve and stressed mice and further uncovered two distinct states in stressed mice. Proteins involved in mitochondrial metabolic functions mostly decreased with chronic stress regardless of the synaptic proteomic state. By contrast, proteins responsible for mitochondrial homeostasis increased in stressed mice with a specific synaptic proteomic state associated with behavioral resilience to chronic stress. These findings suggest that the balance between mitochondrial metabolic dysfunction and its maintenance at mPFC synapses determines stress susceptibility in mice.
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日本薬理学会年会要旨集 95 1-YIA-11 2022年Chronic social stress induces emotional and cognitive disturbances and is a risk for mental illness. Reduced neuronal activity in the medial prefrontal cortex (mPFC) underlies these behavioral abnormalities. However, the subcellular origin and process of this neuronal change remain elusive. Here we examined ultrastructural and multi-omics changes in the mPFC with social stress in mice. Social stress caused the loss of dendritic branches with morphological alterations of mitochondria and induced synaptic shrinkage selectively at mitochondria-containing synapses. Social stress deteriorated mitochondrial functions at synapses with altered mitochondrial proteome and central metabolism in the mPFC. Pharmacological manipulation targeting mitochondria attenuated the synaptic shrinkage and depression-related behaviors. These findings show that chronic social stress alters the central metabolism at mPFC synapses, leading to neuronal pathology and depression-related behaviors.
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日本薬理学会年会要旨集 95 1-SS-43 2022年Aging causes cognitive and motivational declines, but the biological basis remains elusive. Here we analyzed distinct behavioral effects of aging in C57BL6N (B6N) and C57BL/6J (B6J) strains. In this study, mice first learned a visual discrimination task to obtain food rewards by responding to the correct one of two visual stimuli. Then, they learned a response direction task of responding to either left or right for food rewards. Attentional set-shifting, behavioral flexibility between the tasks, is known to depend on working memory. Aged B6N mice showed motivational declines in both tasks. By contrast, task motivation was intact in aged B6J mice, but some of them showed a deficit in attentional set-shifting. We also analyzed synaptic proteomes in the medial prefrontal cortex, a brain region crucial for attentional set-shifting. Young and aged B6J mice showed differential expression of many synaptic proteins, some of which increased only in a subset of the aged mice with attentional set-shifting intact. These findings suggest that different biological mechanisms related to genetic and synaptic factors underlie motivation and cognitive declines with aging.
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日本薬理学会年会要旨集 96 3-B-O06-4 2022年Excessive or chronic social stress induces emotional and cognitive disturbances and precipitates mental illness. Altered neuronal morphology and functions in the medial prefrontal cortex (mPFC) underlie these behavioral abnormalities. However, its subcellular mechanisms remain elusive. Here we examined ultrastructural and multi-omics changes in the mPFC after social stress in mice. Social stress caused the loss of dendritic branches with morphological alterations of subcellular mitochondria and induced synaptic shrinkage selectively at the synapses with mitochondria. Multi-omics and functional analyses revealed that social stress deteriorated mitochondrial functions with altered mitochondrial proteome at synapses and dysregulated central metabolic pathways in the mPFC. Molecular biological and pharmacological manipulation targeting central metabolism and mitochondria attenuated the synaptic shrinkage and depression-related behaviors. These findings demonstrate that chronic social stress alters the central metabolism at mPFC synapses, leading to neuronal pathology and depression-related behaviors.
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Cancer science 103(8) 1378-90 2012年8月 査読有り
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日本癌学会総会記事 70回 485-485 2011年9月
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日本衛生学雑誌 66(3) 562-567 2011年 査読有りSeveral types of fibrous stone called asbestos have been an unexpected cause of human cancer in the history. This form of mineral is considered precious in that they are heat-, friction-, and acid-resistant, are obtained easily from mines, and can be modified to any form with many industrial merits. However, it became evident that the inspiration of asbestos causes a rare cancer called malignant mesothelioma. Because of the long incubation period, the peak year for malignant mesothelioma is expected to be 2025 in Japan. Thus, it is necessary to elucidate the mechanisms of asbestos-induced mesothelial carcinogenesis. In this review, we summarize the cutting edge results of our 5-year project funded by a MEXT grant, in which local iron deposition and the characteristics of mesothelial cells are the key issues.<br>
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Transactions of the Materials Research Society of Japan 36(1) 47-50 2011年 査読有り
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Archives of biochemistry and biophysics 502(1) 1-7 2010年10月1日 査読有り
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日本癌学会総会記事 69回 87-87 2010年8月
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日本癌学会総会記事 69回 140-140 2010年8月
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FREE RADICAL BIOLOGY AND MEDICINE 49 S72-S72 2010年
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肺癌 49(5) 759-759 2009年10月
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日本癌学会総会記事 68回 117-117 2009年8月
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日本癌学会総会記事 68回 135-135 2009年8月
書籍等出版物
2講演・口頭発表等
13-
第50回日本神経精神薬理学会年会、第42回日本生物学的精神医学会年会、第4回日本精神薬学会総会・学術集会 合同年会 2020年8月 招待有り
所属学協会
4共同研究・競争的資金等の研究課題
3-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2020年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 若手研究 2018年4月 - 2021年3月
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日本学術振興会 科学研究費助成事業 特別研究員奨励費 2009年 - 2011年