Molecular mechanisms of the onset of major depressive disorder by regulating both phosphorylation and protein methylation in the white matter of brain
| Project/Area Number |
25430079
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Kinki University |
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Principal Investigator |
MIYATA Shingo 近畿大学, 東洋医学研究所, 准教授 (70403194)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | うつ病 / 脳白質 / 髄鞘 / オリゴデンドロサイト / 慢性ストレス / リン酸化 / タンパクメチル化 / 軸索 / うつ症状 / ランビエ絞輪 |
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| Outline of Final Research Achievements |
Although dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis by chronic stress is indicative of major depression, the molecular mechanisms and functional changes in the brain underlying depression are largely unknown. In this study, by using chronic stress for mice, we attempted to elucidate the molecular pathway induced by elevated plasma corticosterone levels. We observed the following effects both, in vivo and in vitro: (1) repeated exposure to stress activates the 3-phosphoinositide-dependent protein kinase (PDK1)-serum glucocorticoid regulated kinase (SGK1)-N-myc downstream-regulated gene 1 (NDRG1)-adhesion molecule stabilization pathway via an increase in plasma corticosterone levels; and (2) the activation of this signaling pathway induces morphological changes in oligodendrocytes. Our data strongly suggest that these abnornalities of oligodendrocytes are possibly related to depression-like symptoms.
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Report
(4 results)
Research Products
(62 results)
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[Journal Article] Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression.2016
Author(s)
Miyata S, Taniguchi M, Koyama Y, Shimizu S, Tanaka T, Yasuno F, Yamamoto A, Iida H, Kudo T, Katayama T, Tohyama M.
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Journal Title
Sci Rep.
Volume: 6
Issue: 1
Pages: 23084-23084
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] (+)-Catechin protects dermal fibroblasts against oxidative stress-induced apoptosis.2014
Author(s)
Tanigawa T, Kanazawa S, Ichibori R, Fujiwara T, Magome T, Shingaki K, Miyata S, Hata Y, Tomita K, Matsuda K, Kubo T, Tohyama M, Yano K, Hosokawa K.
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Journal Title
BMC Complement. Altern. Med.
Volume: 14(1)
Issue: 1
Pages: 133-133
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] DBZ, a CNS-specific DISC1 binding protein, positively regulates oligodendrocyte differentiation.2014
Author(s)
Shimizu S, Koyama Y, Hattori T, Tachibana T, Yoshimi T, Emoto H, Matsumoto Y, Miyata S, Katayama T, Ito A, Tohyama M.
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Journal Title
Glia.
Volume: 62(5)
Issue: 5
Pages: 709-724
DOI
Related Report
Peer Reviewed
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[Journal Article] XLMR protein related to neurite extension (Xpn/KIAA2022) regulates cell-cell and cell-matrix adhesion and migration2013
Author(s)
Magome T, Hattori T, Taniguchi M, Ishikawa T, Miyata S, Yamada K, Takamura H, Matsuzaki S, Ito A, Tohyama M, Katayama T
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Journal Title
Neurochemistry International
Volume: 63
Issue: 6
Pages: 561-569
DOI
Related Report
Peer Reviewed
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[Journal Article] Suppressive effect of nobiletin, a citrus polymethoxyflavonoid that downregulates thioredoxin-interacting protein expression, on tunicamycin-induced apoptosis in SK-N-SH human neuroblastoma cells.2013
Author(s)
Ikeda A, Nemoto K, Yoshida C, Miyata S, Mori J, Soejima S, Yokosuka A, Mimaki Y, Ohizumi Y, Degawa M.
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Journal Title
Neurosci Lett.
Volume: 549
Pages: 135-9
DOI
Related Report
Peer Reviewed
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[Presentation] 抑肝散の抗ストレス作用2015
Author(s)
清水尚子、宮田信吾、田中貴士、遠山正彌
Organizer
第68回日本自律神経学会総会
Place of Presentation
名古屋 ウインクあいち
Year and Date
2015-10-29
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