System construction to identify the cause of cocaine sensitization using epigenetics analysis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K16648
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Basic / Social brain science
• Research Institution: Kurume University
• Principal Investigator: Ohnishi Yoko 久留米大学, 医学部, 助教 (70727586)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: うつ病 / 依存症 / 転写因子 / エピジェネティクス / 行動実験 / コカイン / AP-1 / プロテアソーム

Outline of Final Research Achievements

We have reported overexpression of deltaFosB in nucleus accumbens worked as anti-depressants, enhanced cocaine addiction after stress, and elevated cocaine sensitization. We tried to find binding partners of deltaFosB by Yeast two hybrid methods, and found several candidates including c-Jun and JunD, which are already known binding partners. We focused on Psmc5 as deltaFosB binding partner, which is one of proteasome machinery. Psmc5 enhanced deltaFosB expression and was induced by cocaine administration. Overexpression of Psmc5 in nucleus accumbens enhanced cocaine sensitization, but deletion form of deltaFosB binding domain of Psmc5 didn’ t have such effects.

Free Research Field

脳神経科学

Academic Significance and Societal Importance of the Research Achievements

依存症やうつ病における脳内の分子的変化と行動に対する影響を明らかにすることで、生物学的に脳の順応反応のメカニズムを明らかにできるところが学術的に意義があります。さらに社会的には、アルコール中毒、たばこ中毒、薬物依存、うつ病といった病気の発症メカニズムを明らかにできることで今後の治療方針、治療薬の開発に役立つ。