2012 Fiscal Year Final Research Report

Establishment of new therapy for the perinatal depression syndrome by regulation of adult hippocampal neurogenesis.

Research Project

Project/Area Number	22500291
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Neuroscience in general
Research Institution	Osaka University
Principal Investigator	KITABATAKE Yasuji 大阪大学, 医学系研究科, 助教 (80506494)
Co-Investigator(Renkei-kenkyūsha)	OTA Akemi 大阪大学, 医学系研究科・小児科, 特任研究員 (20283799)
Project Period (FY)	2010 – 2012
Keywords	うつ病 / 海馬 / 神経新生
Research Abstract	Although major depression is one of the leading causes of morbidity, its mechanisms are not well understood. Here we identified a Wnt signaling inhibitor, secreted frizzled-related protein 3 (sFRP3), as a molecular target of antidepressant treatments in rodent models. Neuronal activity decreases the expression of secreted sFRP3, and sFRP3 deletion activates various step of neurogenesis in the adult mouse hippocampus. Furthermore, in tail-suspension and forced-swimming tests, which are reliable predictors of antidepressant potential, sFRP3 knockout mice showed significantly reduced levels of immobility compared to WT animals. Our studies identify a novel function of sFRP3 as an essential mediator of antidepressant actions in animal models. Targeting of sFRP3 may represent a novel therapeutic approach for depression treatment.