Controlling mechanisms of the serotonergic system by a clock gene Rev-erb alpha relating to bipolar disorder

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K19781
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Psychiatric science
• Research Institution: Wakayama Medical University
• Principal Investigator: Otsuka Tsuyoshi 和歌山県立医科大学, 医学部, 学内助教 (60760395)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 時計遺伝子 / Rev-erbα / セロトニン / 情動障害

Outline of Final Research Achievements

Dysfunction of Rev-erbα, a core circadian clock gene, has been associated with Pathogenesis of affective disorder including bipolar disorder. However, detailed molecular mechanisms remain unclear. In this study, we found dysregulation of serotonergic system in Rev-erbα knockout mice. Despite a reduction in genes expression of key enzymes of serotonin synthesis, knockout mice show normal levels of serotonin and its metabolite in the dorsal raphe nuclei. However, prefrontal cortex, an important target of serotonin, shows the reduction of serotonin levels in knockout animals. These results indicate that serotonin release is impaired in Rev-erbα knockout mice. In addition, the expression of genes related to neuronal activity was decreased in the prefrontal cortex of Rev-erbα knockout mice. Therefore, we have concluded that defect in Rev-erbα may play an important role in organizing the serotonergic system in mammals.

Free Research Field

医歯薬学