Hippocampal microRNA-124 enhances chronic stress resilience in mice
| Project/Area Number |
26860930
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Psychiatric science
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| Research Institution | Yamaguchi University |
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Principal Investigator |
HIGUCHI Fumihiro 山口大学, 医学(系)研究科(研究院), 助教 (60711249)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | microRNA-124 / 気分障害 / うつ病 / 神経可塑性 |
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| Outline of Final Research Achievements |
We examined if altered expression of non-coding microRNAs (miRNAs) contributes to the depression-like behaviors associated with chronic stress.
Mice exposed to chronic ultra-mild stress (CUMS) exhibited increased depression-like behaviors as well as reduced hippocampal expression of the brain-enriched miRNA-124 (miR-124). Aberrant behaviors and dysregulated miR-124 expression were blocked by chronic treatment with an antidepressant drug. Viral-mediated miR-124 overexpression in hippocampal neurons conferred behavioral resilience to CUMS. Moreover, we identified histone deacetylase 4 (HDAC4), HDAC5, and glycogen synthase kinase 3β (GSK3β) as targets for miR-124 and found that intra-hippocampal infusion of a selective HDAC4/5 inhibitor or GSK3 inhibitor had antidepressant-like actions on behavior. We propose that miR-124-mediated post-transcriptional controls of HDAC4/5 and GSK3β expressions in the hippocampus have pivotal roles in susceptibility/resilience to chronic stress.
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Report
(3 results)
Research Products
(2 results)
