Regulation of activity in dorsal raphe nucleus-prefrontal cortex serotonin system

2014 Fiscal Year Final Research Report

• Project/Area Number: 25893274
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Applied pharmacology
• Research Institution: Setsunan University
• Principal Investigator: ARAKI RYOTA 摂南大学, 薬学部, 助教 (90710682)
• Project Period (FY): 2013-08-30 – 2015-03-31
• 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

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.

Free Research Field

神経精神薬理学