The antidepressant roles of Wnt2 and Wnt3 in stress-induced depression-like behaviors.
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.
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.
W-J
WJ
Zhou
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.|Department of Clinical Laboratory, Second Hospital of Shandong University, Jinan, Shandong, China.
N
N
Xu
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.
L
L
Kong
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.
S-C
SC
Sun
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.
X-F
XF
Xu
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.
M-Z
MZ
Jia
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.
Y
Y
Wang
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.
Z-Y
ZY
Chen
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001522:Behavior, Animal; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003863:Depression / Q000235:genetics* / Q000378:metabolism; D005473:Fluoxetine / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D055495:Neurogenesis / Q000235:genetics; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051154:Wnt2 Protein / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D060508:Wnt3 Protein / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism
D018687:Antidepressive Agents, Second-Generation; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D051154:Wnt2 Protein; D060508:Wnt3 Protein; C555508:Wnt3 protein, mouse; D005473:Fluoxetine