A diathesis-stress rat model induced suicide-implicated endophenotypes and prefrontal cortex abnormalities in the PKA and GABA receptor signaling pathways

作者全名："Teng, Teng; Fan, Li; Yan, Wei; Li, Xuemei; Zhang, Yuqing; Xiang, Yajie; Jiang, Yuanliang; Yuan, Kai; Yin, Bangmin; Shi, Le; Liu, Xueer; Yu, Ying; Zhou, Xinyu; Lu, Lin; Xie, Peng"

作者地址："[Teng, Teng; Fan, Li; Xiang, Yajie; Liu, Xueer; Yu, Ying; Xie, Peng] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, 1 Youyi Rd, Chongqing, Peoples R China; [Teng, Teng; Fan, Li; Li, Xuemei; Zhang, Yuqing; Xiang, Yajie; Jiang, Yuanliang; Yin, Bangmin; Liu, Xueer; Yu, Ying; Zhou, Xinyu; Xie, Peng] Chongqing Med Univ, NHC Key Lab Diag & Treatment Brain Funct & Dis, Chongqing, Peoples R China; [Yan, Wei; Yuan, Kai; Shi, Le; Lu, Lin] Peking Univ, Inst Mental Hlth, NHC Key Lab Mental Hlth, Natl Clin Res Ctr Mental Disorders,Hosp 6, Beijing, Peoples R China; [Li, Xuemei; Jiang, Yuanliang; Yin, Bangmin; Zhou, Xinyu] Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, 1 Youyi Rd, Chongqing, Peoples R China; [Zhang, Yuqing] Chongqing Med Univ, Affiliated Hosp 2, Dept Neurol, Chongqing, Peoples R China"

通信作者："Xie, P (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, 1 Youyi Rd, Chongqing, Peoples R China.; Zhou, XY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, 1 Youyi Rd, Chongqing, Peoples R China.; Lu, L (通讯作者)，Peking Univ, Hosp 6, Inst Mental Hlth, 51 Huayuanbei Rd, Beijing, Peoples R China."

来源：PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000819921200005

JCR分区：Q1

影响因子：5.6

年份：2022

卷号：116

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Learned helplessness; Social defeat stress; Suicide; Proteomic analysis

摘要："Suicide is one of the leading causes of death and represents a significant public health problem worldwide; however, the underlying mechanism of suicide remains unclear, and there is no animal model with suicide-implicated endophenotypes for investigating the etiology, course and potential treatment targets of suicide. Thus, we generated a diathesis-stress rat model to simulate suicide-implicated endophenotypes. First, two hundred rats were screened in two rounds of learned helplessness (LH) tests and selected as learned helplessnesssensitive (LHS) rats (n = 37) and learned helplessness-resistant (LHR) rats (n = 39). Then, all LHS rats and half of the rats (randomly selected) in the LHR group were exposed to four weeks of social defeat stress (SDS) (LHS + SDS group, n = 37 and LHR + SDS group, n = 20, respectively). The remainder of the LHR rats were handled as controls (LHR + CON group, n = 19). The LHS + SDS group showed significantly more suicide-implicated endophenotypes than the LHR + CON group, including longer immobile times in the forced swim test (hopelessness), higher scores in the irritability test (irritability), shorter latencies to attack (impulsivity), longer total attack times in the resident-intruder test (aggression), and lower sucrose preference indices (anhedonia). Proteomic analyses revealed that the canonical pathways that were the most common between the LHS + SDS and LHR + CON groups were the PKA and GABA receptor pathways in the prefrontal cortex. A diathesis-stress paradigm would be a useful way to establish a rat model with suicide-implicated endophenotypes, providing novel perspectives for revealing the potential mechanism of suicide."

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]; National Natural Science Foundation of China [81873800, 81820108015]; Chongqing Science and Technology Commission [cstc2020jcyj-jqX0024]; Chongqing Postdoctoral Special Foundation [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 National Natural Science Foundation of China (Grant No. 81820108015 to PX), the National Natural Science Foundation of China (Grant No. 81873800 to XZ), the institutional funds from the Chongqing Science and Technology Commission (Grant No. cstc2020jcyj-jqX0024 to XZ), and the Chongqing Postdoctoral Special Foundation (Grant No. 2010010006132663 to XZ). XZ, LL and PX designed the study. TT, LF, XL, YZ, WY, YX, MQ, BY, XL, YY and XZ conducted the experiments. TT, LF, WY, XZ, LL and PX analyzed the data and wrote and revised the manuscript."