PMID- 34890598
OWN - NLM
STAT- MEDLINE
DCOM- 20220225
LR  - 20220225
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 419
DP  - 2022 Feb 15
TI  - Deep brain stimulation improved depressive-like behaviors and hippocampal synapse 
      deficits by activating the BDNF/mTOR signaling pathway.
PG  - 113709
LID - S0166-4328(21)00597-0 [pii]
LID - 10.1016/j.bbr.2021.113709 [doi]
AB  - Our previous study demonstrated that acute deep brain stimulation (DBS) in the 
      ventromedial prefrontal cortex (vmPFC) remarkably improved the depressive-like 
      behaviors in a rat model of chronic unpredictable mild stress (CUS rats). 
      However, the mechanisms by which chronic DBS altered depressive-like behaviors 
      and reversed cognitive impairment have not been clarified. Recent work has shown 
      that deficits in brain-derived neurotrophic factor (BDNF) and its downstream 
      proteins, including mammalian target of rapamycin (mTOR), might be involved in 
      the pathogenesis of depression. Therefore, we hypothesized that the 
      antidepressant-like and cognitive improvement effects of DBS were achieved by 
      activating the BDNF/mTOR pathway. CUS rats received vmPFC DBS at 20 Hz for 1 h 
      once a day for 28 days. After four weeks of stimulation, the rats were assessed 
      for the presence of depressive-like behaviors and euthanized to detect BDNF/mTOR 
      signaling using immunoblots. DBS at the vmPFC significantly ameliorated 
      depressive-like behaviors and spatial learning and memory deficits in the CUS 
      rats. Furthermore, DBS restored the reduced synaptic density in the hippocampus 
      induced by CUS and increased the expression or activity of BDNF, Akt, and mTOR in 
      the hippocampus. Thus, the antidepressant-like effects and cognitive improvement 
      produced by vmPFC DBS might be mediated through increased activity of the 
      BDNF/mTOR signaling pathway.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Sun, Zuoli
AU  - Sun Z
AD  - The National Clinical Research Center for Mental Disorders & Beijing Key 
      Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical 
      University, Beijing, China.
FAU - Jia, Lina
AU  - Jia L
AD  - The National Clinical Research Center for Mental Disorders & Beijing Key 
      Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical 
      University, Beijing, China.
FAU - Shi, Dandan
AU  - Shi D
AD  - The National Clinical Research Center for Mental Disorders & Beijing Key 
      Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical 
      University, Beijing, China.
FAU - He, Yi
AU  - He Y
AD  - The National Clinical Research Center for Mental Disorders & Beijing Key 
      Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical 
      University, Beijing, China.
FAU - Ren, Yanping
AU  - Ren Y
AD  - The National Clinical Research Center for Mental Disorders & Beijing Key 
      Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical 
      University, Beijing, China.
FAU - Yang, Jian
AU  - Yang J
AD  - The National Clinical Research Center for Mental Disorders & Beijing Key 
      Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical 
      University, Beijing, China; Advanced Innovation Center for Human Brain 
      Protection, Capital Medical University, Beijing, China. Electronic address: 
      yangjian@ccmu.edu.cn.
FAU - Ma, Xin
AU  - Ma X
AD  - The National Clinical Research Center for Mental Disorders & Beijing Key 
      Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical 
      University, Beijing, China; Advanced Innovation Center for Human Brain 
      Protection, Capital Medical University, Beijing, China. Electronic address: 
      maxinanding@ccmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211208
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - 0 (Bdnf protein, rat)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/physiology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cognitive Dysfunction/metabolism/*therapy
MH  - *Deep Brain Stimulation
MH  - Depression/metabolism/*therapy
MH  - Disease Models, Animal
MH  - Hippocampus/metabolism/*physiology
MH  - Male
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stress, Psychological/metabolism/*therapy
MH  - Synapses/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Deep brain stimulation
OT  - Depression
OT  - Mammalian target of rapamycin
OT  - Synapse
EDAT- 2021/12/11 06:00
MHDA- 2022/02/26 06:00
CRDT- 2021/12/10 20:13
PHST- 2021/05/27 00:00 [received]
PHST- 2021/11/18 00:00 [revised]
PHST- 2021/12/06 00:00 [accepted]
PHST- 2021/12/11 06:00 [pubmed]
PHST- 2022/02/26 06:00 [medline]
PHST- 2021/12/10 20:13 [entrez]
AID - S0166-4328(21)00597-0 [pii]
AID - 10.1016/j.bbr.2021.113709 [doi]
PST - ppublish
SO  - Behav Brain Res. 2022 Feb 15;419:113709. doi: 10.1016/j.bbr.2021.113709. Epub 
      2021 Dec 8.