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Transl Psychiatry. 2016 Sep 13;6(9):e892. doi: 10.1038/tp.2016.122.

The antidepressant roles of Wnt2 and Wnt3 in stress-induced depression-like behaviors.

Author information

1
Department of Neurobiology, Shandong Provincial Key Laboratory of Mental Disorders, CAS Center for Excellence in Brain Science and Intelligence Technology, School of Medicine, Shandong University, Jinan, Shandong, China.
2
Department of Clinical Laboratory, Second Hospital of Shandong University, Jinan, Shandong, China.

Abstract

Wnts-related signaling pathways have been reported to play roles in the pathogenesis of stress-induced depression-like behaviors. However, there is relatively few direct evidence to indicate the effect of Wnt ligands on this process. Here, we investigated the role of Wnts in mediating chronic restraint stress (CRS)-induced depression-like behaviors. We found that CRS induced a significant decrease in the expression of Wnt2 and Wnt3 in the ventral hippocampus (VH) but not in the dorsal hippocampus. Knocking down Wnt2 or Wnt3 in the VH led to impaired Wnt/β-catenin signaling, neurogenesis deficits and depression-like behaviors. In contrast, overexpression of Wnt2 or Wnt3 reversed CRS-induced depression-like behaviors. Moreover, Wnt2 and Wnt3 activated cAMP response element-binding protein (CREB) and there was CREB-dependent positive feedback between Wnt2 and Wnt3. Finally, fluoxetine treatment increased Wnt2 and Wnt3 levels in the VH and knocking down Wnt2 or Wnt3 abolished the antidepressant effect of fluoxetine. Taken together, our study indicates essential roles for Wnt2 and Wnt3 in CRS-induced depression-like behaviors and antidepressant.

PMID:
27622936
PMCID:
PMC5048193
DOI:
10.1038/tp.2016.122
[Indexed for MEDLINE]
Free PMC Article

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