| Project/Area Number |
25893274
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Applied pharmacology
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| Research Institution | Setsunan University |
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Principal Investigator |
ARAKI RYOTA 摂南大学, 薬学部, 助教 (90710682)
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| Project Period (FY) |
2013-08-30 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 背側縫線核 / GABAB受容体 / エピジェネティクス / 環境要因 / 精神疾患 / DNAメチル化 / ヒストンアセチル化 / 環境因子 / GABAB / セロトニン / グルタミン酸神経 / GABA神経 |
|---|
| Outline of Final Research Achievements |
Adverse environments are likely to induce abnormalities in brain function via epigenetic modifications. In this study, we examined epigenetic mechanisms underlying abnormal behaviors of isolation-reared mice. Both mRNA and protein levels of GABAB1a, a GABAB receptor subunit, were increased in the dorsal raphe nucleus (DRN) of isolation-reared mice. Total DNA methylation level at the CpG island of GABAB1a was decreased, and histone H3 was hyperacetylated at a GABAB1a promoter in the DRN of isolation-reared mice. Intra-DRN microinjection of 0.06 nmol baclofen (a GABAB receptor agonist) exacerbated encounter-induced hyperactivity, while microinjection of 0.3 nmol phaclofen (a GABAB receptor antagonist) attenuated encounter-induced hyperactivity and aggressive behavior in isolation-reared mice. These findings suggest that an increase in dorsal raphe GABAB1a expression via DNA hypomethylation and histone H3 hyperacetylation underlies abnormal behaviors in isolation-reared mice.
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