PMID- 33639208
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20210927
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 340
DP  - 2021 Jun
TI  - PPM1F in hippocampal dentate gyrus regulates the depression-related behaviors by 
      modulating neuronal excitability.
PG  - 113657
LID - S0014-4886(21)00062-5 [pii]
LID - 10.1016/j.expneurol.2021.113657 [doi]
AB  - Major depressive disorder (MDD) is a common, serious, debilitating mental 
      illness. Protein phosphatase Mg(2+)/Mn(2+)-dependent 1F (PPM1F), a 
      serine/threonine phosphatase, has been reported to have multiple biological and 
      cellular functions. However, the effects of PPM1F and its neuronal substrates on 
      depressive behaviors remain largely unknown. Here, we showed that PPM1F is widely 
      distributed in the hippocampus, and chronic unpredictable stress (CUS) can induce 
      increased expression of PPM1F in the hippocampus, which was correlated with 
      depression-associated behaviors. Overexpression of PPM1F mediated by 
      adeno-associated virus (AAV) in the dentate gyrus (DG) produced 
      depression-related behaviors and enhanced susceptibility to subthreshold CUS 
      (SCUS) in both male and female mice, while, knockout of PPM1F in DG produced 
      antidepressant phonotypes under stress conditions. Whole-cell patch-clamp 
      recordings demonstrated that overexpression of PPM1F increased the neuronal 
      excitability of the granule cells in the DG. Consistent with neuronal 
      hyperexcitability, overexpression of PPM1F regulated the expression of certain 
      ion channel genes and induced decreased phosphorylation of 
      Ca2+/calmodulin-dependent protein kinase II (CAMKII) and Adenosine 
      5'-monophosphate (AMP)-activated protein kinase (AMPK) in hippocampus. These 
      results suggest that PPM1F in the DG regulates depression-related behaviors by 
      modulating neuronal excitability, which might be an important pathological gene 
      for depression or other mental diseases.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Liu, Jing
AU  - Liu J
AD  - Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University 
      Hospital, Binzhou, Shandong, China.
FAU - Meng, Fantao
AU  - Meng F
AD  - Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University 
      Hospital, Binzhou, Shandong, China.
FAU - Wang, Wentao
AU  - Wang W
AD  - Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University 
      Hospital, Binzhou, Shandong, China.
FAU - Cui, Minghu
AU  - Cui M
AD  - Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong, 
      China.
FAU - Wu, Min
AU  - Wu M
AD  - Neurosurgery, Binzhou Medical University Hospital, Binzhou, Shandong, China.
FAU - Jiang, Shujun
AU  - Jiang S
AD  - Department of Physiology, Binzhou Medical University, Yantai, China.
FAU - Dai, Juanjuan
AU  - Dai J
AD  - Cancer Research Institute, Binzhou Medical University Hospital, Binzhou, 
      Shandong, China.
FAU - Lian, Haifeng
AU  - Lian H
AD  - Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, 
      Shandong, China.
FAU - Li, Qiongyu
AU  - Li Q
AD  - Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, 
      Shandong, China.
FAU - Xu, Zhicheng
AU  - Xu Z
AD  - Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University 
      Hospital, Binzhou, Shandong, China.
FAU - Wang, Yameng
AU  - Wang Y
AD  - Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University 
      Hospital, Binzhou, Shandong, China.
FAU - Zhang, Jingyan
AU  - Zhang J
AD  - Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University 
      Hospital, Binzhou, Shandong, China.
FAU - Li, Chen
AU  - Li C
AD  - Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University 
      Hospital, Binzhou, Shandong, China. Electronic address: lc_0625@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210224
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - EC 3.1.3.16 (PPM1F protein, mouse)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
SB  - IM
MH  - Animals
MH  - Dentate Gyrus/*metabolism
MH  - Depression/genetics/*metabolism/psychology
MH  - Female
MH  - Locomotion/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/*metabolism
MH  - Phosphoprotein Phosphatases/*biosynthesis/genetics
OTO - NOTNLM
OT  - Chronic unpredictable stress
OT  - Dentate gyrus
OT  - Depression-related behaviors
OT  - Neuronal excitability
OT  - PPM1F
EDAT- 2021/02/28 06:00
MHDA- 2021/09/28 06:00
CRDT- 2021/02/27 20:08
PHST- 2020/08/11 00:00 [received]
PHST- 2020/12/28 00:00 [revised]
PHST- 2021/02/21 00:00 [accepted]
PHST- 2021/02/28 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2021/02/27 20:08 [entrez]
AID - S0014-4886(21)00062-5 [pii]
AID - 10.1016/j.expneurol.2021.113657 [doi]
PST - ppublish
SO  - Exp Neurol. 2021 Jun;340:113657. doi: 10.1016/j.expneurol.2021.113657. Epub 2021 
      Feb 24.