PMID- 28798340
OWN - NLM
STAT- MEDLINE
DCOM- 20190226
LR  - 20190226
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Aug 10
TI  - Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory 
      Extinction in Adulthood.
PG  - 7857
LID - 10.1038/s41598-017-08017-7 [doi]
LID - 7857
AB  - Early-life stress in adolescence has a long-lasting influence on brain function 
      in adulthood, and it is mostly recognized as a predisposing factor for mental 
      illnesses, such as anxiety and posttraumatic stress disorder. Previous studies 
      also indicated that adolescent predictable chronic mild stress (PCMS) in early 
      life promotes resilience to depression- and anxiety-like behaviors in adulthood. 
      However, the role of PCMS in associated memory process is still unclear. In the 
      present study, we found that adolescent PCMS facilitated extinction and inhibited 
      fear response in reinstatement and spontaneous recovery tests in adult rats, and 
      this effect was still present 1 week later. PCMS in adolescence increased the 
      activity of brain-derived neurotrophic factor (BDNF)-extracellular 
      signal-regulated kinase 1/2 (ERK1/2) signaling in infralimbic cortex (IL) but not 
      prelimbic cortex in adulthood. Intra-IL infusion of BDNF antibody and the ERK1/2 
      inhibitor U0126 reversed PCMS-induced enhancement of fear extinction. Moreover, 
      we found that PCMS decreased DNA methylation of the Bdnf gene at exons IV and VI 
      and elevated the mRNA levels of Bdnf in the IL. Our findings indicate that 
      adolescent PCMS exposure promotes fear memory extinction in adulthood, which 
      reevaluates the traditional notion of adolescent stress.
FAU - Deng, Jia-Hui
AU  - Deng JH
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China.
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China.
FAU - Yan, Wei
AU  - Yan W
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China.
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China.
AD  - School of Basic Medical Sciences, Peking University Health Science Center, 
      Beijing, 100191, China.
FAU - Han, Ying
AU  - Han Y
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China. yinghan@bjmu.edu.cn.
FAU - Chen, Chen
AU  - Chen C
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China.
FAU - Meng, Shi-Qiu
AU  - Meng SQ
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China.
FAU - Sun, Cheng-Yu
AU  - Sun CY
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China.
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China.
FAU - Xu, Ling-Zhi
AU  - Xu LZ
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China.
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China.
FAU - Xue, Yan-Xue
AU  - Xue YX
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China.
FAU - Gao, Xue-Jiao
AU  - Gao XJ
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China.
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China.
FAU - Chen, Na
AU  - Chen N
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China.
FAU - Zhang, Fei-Long
AU  - Zhang FL
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China.
FAU - Wang, Yu-Mei
AU  - Wang YM
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China.
AD  - Department of Mental Health, First Hospital of Hebei Medical University, Hebei 
      Medical University, Shijiazhuang, 050031, China.
FAU - Shi, Jie
AU  - Shi J
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China. shijie@bjmu.edu.cn.
FAU - Lu, Lin
AU  - Lu L
AD  - National Institute on Drug Dependence and Beijing Key Laboratory of Drug 
      Dependence, Peking University, Beijing, 100191, China. linlu@bjmu.edu.cn.
AD  - Peking University Sixth Hospital, Peking University Institute of Mental Health, 
      Key Laboratory of Mental Health, Ministry of Health (Peking University), National 
      Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), 
      Peking University, Beijing, 100191, China. linlu@bjmu.edu.cn.
AD  - Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain 
      Research, Peking University, Beijing, 100871, China. linlu@bjmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170810
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Extinction, Psychological
MH  - *Fear
MH  - Limbic System/physiology
MH  - MAP Kinase Signaling System
MH  - *Memory
MH  - Rats, Sprague-Dawley
MH  - *Stress, Psychological
PMC - PMC5552791
COIS- The authors declare that they have no competing interests.
EDAT- 2017/08/12 06:00
MHDA- 2019/02/27 06:00
PMCR- 2017/08/10
CRDT- 2017/08/12 06:00
PHST- 2017/04/06 00:00 [received]
PHST- 2017/07/03 00:00 [accepted]
PHST- 2017/08/12 06:00 [entrez]
PHST- 2017/08/12 06:00 [pubmed]
PHST- 2019/02/27 06:00 [medline]
PHST- 2017/08/10 00:00 [pmc-release]
AID - 10.1038/s41598-017-08017-7 [pii]
AID - 8017 [pii]
AID - 10.1038/s41598-017-08017-7 [doi]
PST - epublish
SO  - Sci Rep. 2017 Aug 10;7(1):7857. doi: 10.1038/s41598-017-08017-7.