Deletion of TRIM32 protects mice from anxiety- and depression-like behaviors under mild stress.
Chronic stress causes a variety of psychiatric disorders such as anxiety and depression, but its mechanism is not well understood. Tripartite motif-containing protein 32 (TRIM32) was strongly associated with autism spectrum disorder, attention deficit hyperactivity disorder, anxiety and obsessive compulsive disorder based on a study of copy number variation, and deletion of TRIM32 increased neural proliferation and reduced apoptosis. Here, we propose that TRIM32 is involved in chronic stress-induced affective behaviors. Using a chronic unpredictable mild stress mouse depression model, we studied expression of TRIM32 in brain tissue samples and observed behavioral changes in Trim32 knockout mice. The results showed that TRIM32 protein but not its mRNA was significantly reduced in hippocampus in a time-dependent manner within 8 weeks of chronic stress. These stress-induced affective behaviors and reduction of TRIM32 protein expression were significantly reversed by antidepressant fluoxetine treatment. In addition, Trim32 knockout mice showed reduced anxiety and depressive behaviors and hyperactivities compared with Trim32 wild-type mice under normal and mild stress conditions. We conclude that TRIM32 plays important roles in regulation of hyperactivities and positively regulates the development of anxiety and depression disorders induced by chronic stress.
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming, China; Division of Health Sciences, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5000, Australia.
Chun-Sheng
CS
Ruan
Shu-Fen
SF
Wang
Yan-Jun
YJ
Shen
Yi
Y
Guo
Chun-Rui
CR
Yang
Fiona H
FH
Zhou
Li-Tao
LT
Tan
Li
L
Zhou
Jian-Jun
JJ
Liu
Wen-Yue
WY
Wang
Zhi-Cheng
ZC
Xiao
Xin-Fu
XF
Zhou
D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D017353:Gene Deletion; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D013315:Stress, Psychological / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
C514011:TRIM32 protein, mouse; D044767:Ubiquitin-Protein Ligases
CUMS; TRIM32; affective behavior; fluoxetine; locomotor activity