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Predictable Chronic Mild Stress during Adolescence Promotes Fear Memory Extinction in Adulthood.

Abstract：

: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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Deng JH,Yan W,Han Y,Chen C,Meng SQ,Sun CY,Xu LZ,Xue YX,Gao XJ,Chen N,Zhang FL,Wang YM,Shi J,Lu L

doi

10.1038/s41598-017-08017-7

subject

Has Abstract

pub_date

2017-08-10 00:00:00

pages

7857

issue

1

issn

2045-2322

pii

10.1038/s41598-017-08017-7

journal_volume

7

pub_type

杂志文章

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