Mice deficient for wild-type p53-induced phosphatase 1 display elevated anxiety- and depression-like behaviors.
Mood disorders are a severe health burden but molecular mechanisms underlying mood dysfunction remain poorly understood. Here, we show that wild-type p53-induced phosphatase 1 (Wip1) negatively responds to the stress-induced negative mood-related behaviors. Specifically, we show that Wip1 protein but not its mRNA level was downregulated in the hippocampus but not in the neocortex after 4 weeks of chronic unpredictable mild stress (CUMS) in mice. Moreover, the CUMS-responsive WIP1 downregulation in the hippocampus was restored by chronic treatment of fluoxetine (i.p. 20 mg/kg) along with the CUMS procedure. In addition, Wip1 knockout mice displayed decreased exploratory behaviors as well as increased anxiety-like and depression-like behaviors in mice without impaired motor activities under the non-CUMS condition. Furthermore, the Wip1 deficiency-responsive anxiety-like but not depression-like behaviors were further elevated in mice under CUMS. Although limitations like male-alone sampling and multiply behavioral testing exist, the present study suggests a potential protective function of Wip1 in mood stabilization.
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China; School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia. Electronic address: chunsheng.ruan@mymail.unisa.edu.au.
C S
CS
Ruan
School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia; School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, SA 5001, Australia.
F H
FH
Zhou
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China; MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, PR China.
Z Y
ZY
He
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China.
S F
SF
Wang
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China; Department of Pathology, Second Hospital of Tianjin Medical University, Tianjin 300000, PR China.
C R
CR
Yang
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China.
Y J
YJ
Shen
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China.
Y
Y
Guo
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China.
H B
HB
Zhao
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China.
L
L
Chen
Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA 5000, Australia; Mental Health Service, Northern Adelaide Local Health Network, Adelaide, SA 5000, Australia.
D
D
Liu
School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
J
J
Liu
Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA 5000, Australia.
B T
BT
Baune
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China; Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.
Z C
ZC
Xiao
Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650500, PR China; School of Pharmacy and Medical Sciences, Division of Health Sciences, University of South Australia, Adelaide, SA 5000, Australia.
X F
XF
Zhou
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology; D003863:Depression / Q000378:metabolism* / Q000503:physiopathology; D005106:Exploratory Behavior / Q000502:physiology; D005473:Fluoxetine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D000071636:Protein Phosphatase 2C; D012333:RNA, Messenger / Q000378:metabolism; D013315:Stress, Psychological / Q000378:metabolism / Q000503:physiopathology
D018687:Antidepressive Agents, Second-Generation; D012333:RNA, Messenger; D005473:Fluoxetine; D010749:Phosphoprotein Phosphatases; C000607468:Ppm1d protein, mouse; D000071636:Protein Phosphatase 2C
CUMS; Wip1; anxiety-like behavior; depression-like behavior; exploratory behavior; fluoxetine