| 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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