Integrative research on mood and clock

2015 Fiscal Year Final Research Report

• Project/Area Number: 25242077
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Takumi Toru 国立研究開発法人理化学研究所, 脳科学総合研究センター, シニアチームリーダー (00222092)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 概日リズム / 気分障害 / 時計遺伝子 / リン酸化

Outline of Final Research Achievements

Dysfunction of mood and the circadian clock together represent a large proportion of mental illness with adverse economic impact. Clinical and genetic evidence indicates that the two disorders are co-regulated but direct molecular evidence is lacking. We showed that GSK3β phosphorylation of PER2 is essential for co-regulation of mood and the circadian clock. In rodent depression models, we observed defective circadian rhythms associated with the loss of synchronized phosphorylation of GSK3β. Both molecular and behavioral phenotypes were restored by lithium, a mood stabilizer. GSK3β phosphorylation in PER2 was essential for both mood and circadian behaviors. Strikingly, Per2 mutant mice were resistant to both lithium and learned helplessness, a depression model. Together, these findings show that mood and the circadian clock share a coherent molecular mechanism and reveal the potential for synchronized drug and behavioral therapy of mood and circadian disorders.

Free Research Field

脳科学