Maternal separation regulates sensitivity of stress-induced depression in mice by affecting hippocampal metabolism

作者全名：Zhang, Yangdong; Wang, Haiyang; Liu, Lanxiang; Mo, Xiaolong; He, Dian; Chen, Xueyi; Xiao, Rui; Cheng, Qisheng; Fatima, Madiha; Du, Yamei; Xie, Peng

作者地址：[Zhang, Yangdong; Wang, Haiyang; Liu, Lanxiang; Mo, Xiaolong; He, Dian; Chen, Xueyi; Xiao, Rui; Cheng, Qisheng; Fatima, Madiha; Du, Yamei; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, 1 Youyi Rd, Chongqing 400016, Peoples R China; [Zhang, Yangdong; Mo, Xiaolong; He, Dian; Cheng, Qisheng; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing 400016, Peoples R China; [Liu, Lanxiang; Xie, Peng] Chongqing Med Univ, Dept Neurol, Yongchuan Hosp, Chongqing 402160, Peoples R China; [Chen, Xueyi; Xiao, Rui] Chongqing Med Univ, Fac Basic Med, Dept Pathol, Chongqing 400016, Peoples R China

通信作者：Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, NHC Key Lab Diag & Treatment Brain Funct Dis, 1 Youyi Rd, Chongqing 400016, Peoples R China.

来源：PHYSIOLOGY & BEHAVIOR

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001227019600001

JCR分区：Q2

影响因子：2.4

年份：2024

卷号：279

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Early life stress; Maternal separation; Depression; Metabolism; Hippocampus

摘要：Depression is a serious mental illness. Previous studies found that early life stress (ELS) plays a vital role in the onset and progression of depression. However, relevant studies have not yet been able to explain the specific effects of early stress on stress-induced depression sensitivity and individual behavior during growth. Therefore, we constructed a maternal separation (MS) model and administered chronic social frustration stress at different stages of their growth while conducting metabolomics analysis on the hippocampus of mice. Our results showed that the immobility time of mice in the forced swimming test was significantly reduced at the end of MS. Meanwhile, mice with MS experience significantly decreased total movement distance in the open field test and sucrose preference ratio in the sucrose preference test when subjected to chronic social defeat stress (CSDS) during adolescence. In adulthood, the results were the opposite. In addition, we found that level changes in metabolites such as Beta-alanine, l-aspartic acid, 2-aminoadipic acid, and Glycine are closely related to behavioral changes. These metabolites are mainly enriched in Pantothenate, CoA biosynthesis, and Beta Alanine metabolism pathways. Our experiment revealed that the effects of ELS vary across different age groups. It will increase an individual's sensitivity to depression when facing CSDS in adolescence, but it will reduce their sensitivity to depression when facing CSDS in adulthood. This may be achieved by regulating the hippocampus's Pantothenate and CoA biosynthesis and Beta Alanine metabolism pathways represented by Beta-alanine, lAspartic acid, 2-aminoadipic acid, and Glycine metabolites.

基金机构：Joint Project of Chongqing Municipal Science and Technology Bureau and Chongqing Health Commission [2023CCXM003]; National Key Research and Development Program of China [2017YFA0505700]; Natural Science Foundation Project of China [82201683]

基金资助正文：This work was supported by a grant from the Joint Project of Chongqing Municipal Science and Technology Bureau and Chongqing Health Commission (2023CCXM003) , National Key Research and Development Program of China (2017YFA0505700) and the Natural Science Foundation Project of China (No. 82201683) .