Molecular and neural mechanisms of depression

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04895
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Psychiatric science
• Research Institution: Yamaguchi University
• Principal Investigator: WATANABE Yoshifumi 山口大学, 大学院医学系研究科, 教授(特命) (90182964)
• 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)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ストレス / うつ病 / エピジェネティクス

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.

Free Research Field

精神医学