Pathophysiology underlying depressive-like behaviors and sleep disturbance
| Project/Area Number |
26430008
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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 |
Neurophysiology / General neuroscience
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| Research Institution | Hiroshima University (2015-2016)
Tokyo Medical and Dental University (2014) |
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Principal Investigator |
Aizawa Hidenori 広島大学, 医歯薬保健学研究院(医), 教授 (80391837)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | うつ病 / 睡眠 / モノアミン / 手綱核 / グルタミン酸 / 輸送体 / グリア細胞 |
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| Outline of Final Research Achievements |
We examined the activity of neurons in habenular pathways and performed behavioral and sleep analyses in mice with pharmacological and genetic inhibition of the activity of the glial glutamate transporter GLT-1 in the LHb. The habenula-specific inhibition of GLT-1 increased the neuronal firing rate and the level of c-Fos expression in the LHb. Mice with reduced GLT-1 activity in the habenula exhibited a depressive-like phenotype in the tail suspension and novelty-suppressed feeding tests. These animals also displayed increased susceptibility to chronic stress, displaying more frequent avoidant behavior without affecting locomotor activity in the open-field test. Intriguingly, the mice showed disinhibition of rapid eye movement sleep, which is a characteristic sleep pattern in patients with depression. These results provide evidence that disrupting glutamate clearance in habenular astrocytes increases neuronal excitability and depressive-like phenotypes in behaviors and sleep.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Gene cassette knock-in in mammalian cells and zygotes by enhanced MMEJ.2016
Author(s)
Aida T, Nakade S, Sakuma T, Izu Y, Oishi A, Mochida K, Ishikubo H, Usami T, Aizawa H, Yamamoto T, Tanaka K.
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Journal Title
BMC Genomics
Volume: 17
Issue: 1
Pages: 979-979
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Impaired striatal dopamine release in homozygous Vps35 D620N knock-in mice.2016
Author(s)
Ishizu N, Yui D, Hebisawa A, Aizawa H, Cui W, Fujita Y, Hashimoto K, Ajioka I, Mizusawa H, Yokota T, Watase K.
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Journal Title
Hum Mol Genet
Volume: 25
Pages: 4507-4517
DOI
Related Report
Peer Reviewed
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