AKT and MAPK signaling pathways in hippocampus reveals the pathogenesis of depression in four stress-induced models

作者全名："Li, Xuemei; Teng, Teng; Yan, Wei; Fan, Li; Liu, Xueer; Clarke, Gerard; Zhu, Dan; Jiang, Yuanliang; Xiang, Yajie; Yu, Ying; Zhang, Yuqing; Yin, Bangmin; Lu, Lin; Zhou, Xinyu; Xie, Peng"

作者地址："[Li, Xuemei; Teng, Teng; Jiang, Yuanliang; Yin, Bangmin; Zhou, Xinyu] Chongqing Med Univ, Dept Psychiat, Affiliated Hosp 1, Chongqing, Peoples R China; [Li, Xuemei; Teng, Teng; Fan, Li; Liu, Xueer; Jiang, Yuanliang; Xiang, Yajie; Yu, Ying; Zhang, Yuqing; Yin, Bangmin; Zhou, Xinyu; Xie, Peng] Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing, Peoples R China; [Yan, Wei; Lu, Lin] Peking Univ, Peking Univ Sixth Hosp, Inst Mental Hlth, Beijing, Peoples R China; [Fan, Li; Liu, Xueer; Zhu, Dan; Xiang, Yajie; Yu, Ying; Xie, Peng] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China; [Clarke, Gerard] Univ Coll Cork, Dept Psychiat & Neurobehav Sci, Cork, Ireland; [Clarke, Gerard] Univ Coll Cork, APC Microbiome Ireland, Cork, Ireland; [Zhang, Yuqing] Chongqing Med Univ, Dept Neurol, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："Zhou, XY (通讯作者)，Chongqing Med Univ, Dept Psychiat, Affiliated Hosp 1, Chongqing, Peoples R China.; Zhou, XY; Xie, P (通讯作者)，Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct Dis, Affiliated Hosp 1, Chongqing, Peoples R China.; Lu, L (通讯作者)，Peking Univ, Peking Univ Sixth Hosp, Inst Mental Hlth, Beijing, Peoples R China.; Xie, P (通讯作者)，Chongqing Med Univ, Dept Neurol, Affiliated Hosp 1, Chongqing, Peoples R China."

来源：TRANSLATIONAL PSYCHIATRY

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:001004954200001

JCR分区：Q1

影响因子：5.8

年份：2023

卷号：13

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Major depressive disorder (MDD) is a highly heterogeneous psychiatric disorder. The pathogenesis of MDD remained unclear, and it may be associated with exposure to different stressors. Most previous studies have focused on molecular changes in a single stress-induced depression model, which limited the identification of the pathogenesis of MDD. The depressive-like behaviors were induced by four well-validated stress models in rats, including chronic unpredictable mild stress, learned helplessness stress, chronic restraint stress and social defeat stress. We applied proteomic and metabolomic to investigate molecular changes in the hippocampus of those four models and revealed 529 proteins and 98 metabolites. Ingenuity Pathways Analysis (IPA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified differentially regulated canonical pathways, and then we presented a schematic model that simulates AKT and MAPK signaling pathways network and their interactions and revealed the cascade reactions. Further, the western blot confirmed that p-AKT, p-ERK12, GluA1, p-MEK1, p-MEK2, p-P38, Syn1, and TrkB, which were changed in at least one depression model. Importantly, p-AKT, p-ERK12, p-MEK1 and p-P38 were identified as common alterations in four depression models. The molecular level changes caused by different stressors may be dramatically different, and even opposite, between four depression models. However, the different molecular alterations converge on a common AKT and MAPK molecular pathway. Further studies of these pathways could contribute to a better understanding of the pathogenesis of depression, with the ultimate goal of helping to develop or select more effective treatment strategies for MDD."

基金机构：National Key Research and Development Program of China [2017YFA0505700]; Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2019PT320002]; Natural Science Foundation Project of China [81820108015]; National Natural Science Foundation of China [81873800290]; Chongqing Science and Technology Commission [291 cstc2020jcyj-jqX0024]; Chongqing Postdoctoral Special Foundation [292 2010010006132663]

基金资助正文："This work was financially supported by The National Key Research and Development Program of China (Grant No. 2017YFA0505700 to PX), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (Grant No. 2019PT320002 to PX), the Natural Science Foundation Project of China (Grant No. 81820108015 to PX), the National Natural Science Foundation of China (Grant No. 81873800290 to XZ), the institutional funds from the Chongqing Science and Technology Commission (Grant No. 291 cstc2020jcyj-jqX0024 to XZ), and Chongqing Postdoctoral Special Foundation (Grant No. 292 2010010006132663 to XZ)."