Molecular and neural mechanisms of depression
| Project/Area Number |
15H04895
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
内田 周作 山口大学, 医学部附属病院, 講師 (10403669)
山形 弘隆 山口大学, 医学部附属病院, 講師 (10549934)
樋口 文宏 山口大学, 大学院医学系研究科, 助教 (60711249)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2016: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2015: ¥9,360,000 (Direct Cost: ¥7,200,000、Indirect Cost: ¥2,160,000)
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| Keywords | ストレス / うつ病 / エピジェネティクス / うつ / 遺伝子発現 / 神経ネットワーク / ストレス脆弱性 / HDAC / CaMKII |
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| Outline of Final Research Achievements |
This study aims to elucidate molecular and neural mechanisms of depression. To this end, we used an animal model of depression and analyzed the levels of a variety of mRNA. We found altered expression of CaMKIIbeta and HDAC4 in the hippocampus and medial prefrontal cortex, respectively. Viral-mediated gene transfer experiment revealed that these two molecules are critically involved in depression-like behaviors. In addition, gain- and loss-of-function CaMKIIbeta and HDAC4 within the hippocampus and medial prefrontal cortex affect neural activity in the nucleus accumbens, suggesting that neural networks from the hippocampus and medial prefrontal cortex to the nucleus accumbens may be associated with depressed symptom. Indeed, we used DREADDs technology to selectively inactivate these neural networks and found an altered behavioral response to chronic stress in mice.
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] CRTC1 Nuclear Translocation Following Learning Modulates Memory Strength via Exchange of Chromatin Remodeling Complexes on the Fgf1 Gene.2017
Author(s)
Uchida S, Teubner BJ, Hevi C, Hara K, Kobayashi A, Dave RM, Shintaku T, Jaikhan P, Yamagata H, Suzuki T, Watanabe Y, Zakharenko SS, Shumyatsky GP.
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Journal Title
Cell Rep
Volume: 18
Issue: 2
Pages: 352-366
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hippocampal MicroRNA-124 Enhances Chronic Stress Resilience in Mice.2016
Author(s)
Higuchi F, Uchida S, Yamagata H, Abe-Higuchi N, Hobara T, Hara K, Kobayashi A, Shintaku T, Itoh Y, Suzuki T, Watanabe Y.
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Journal Title
J Neurosci.
Volume: 36
Issue: 27
Pages: 7253-7267
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Genetic Demonstration of a Role for Stathmin in Adult Hippocampal Neurogenesis, Spinogenesis, and NMDA Receptor-Dependent Memory2016
Author(s)
Martel G, Uchida S, Hevi C, Chevere-Torres I, Fuentes I, Park YJ, Hafeez H, Yamagata H, Watanabe Y, Shumyatsky GP
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Journal Title
J Neurosci
Volume: 36
Issue: 4
Pages: 1185-1202
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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