Neuronal ablation of GHSR mitigates diet-induced depression and memory impairment via AMPK-autophagy signaling-mediated inflammation

作者全名："Wang, Hongying; Shen, Zheng; Wu, Chia-Shan; Ji, Pengfei; Noh, Ji Yeon; Geoffroy, Cedric G.; Kim, Sunja; Threadgill, David; Li, Jianrong; Zhou, Yu; Xiao, Xiaoqiu; Zheng, Hui; Sun, Yuxiang"

作者地址："[Wang, Hongying; Shen, Zheng; Wu, Chia-Shan; Ji, Pengfei; Noh, Ji Yeon; Threadgill, David; Sun, Yuxiang] Texas A&M Univ, Dept Nutr, College Stn, TX 77843 USA; [Wang, Hongying; Xiao, Xiaoqiu] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Translat Med Major Metab Dis, First Affiliated Hosp, Chongqing, Peoples R China; [Geoffroy, Cedric G.] Texas A&M Univ, Dept Neurosci & Expt Therapeut, College Stn, TX USA; [Kim, Sunja; Threadgill, David] Texas A&M Univ, Texas A&M Inst Genome Sci & Soc, College Stn, TX USA; [Threadgill, David] Texas A&M Univ, Dept Mol & Cellular Med, College Stn, TX USA; [Li, Jianrong] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA; [Zhou, Yu] Univ Hlth & Rehabil Sci, Dept Hlth & Life Sci, Qingdao, Shandong, Peoples R China; [Zheng, Hui] Baylor Coll Med, Huffington Ctr Aging, Houston, TX USA"

通信作者："Sun, YX (通讯作者)，Texas A&M Univ, Dept Nutr, College Stn, TX 77843 USA."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001177010100001

JCR分区：Q1

影响因子：5.7

年份：2024

卷号：15

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：obesity; behaviors; neuroinflammation; GHSR; AMPK; autophagy

摘要："Obesity is associated with chronic inflammation in the central nervous system (CNS), and neuroinflammation has been shown to have detrimental effects on mood and cognition. The growth hormone secretagogue receptor (GHSR), the biologically relevant receptor of the orexigenic hormone ghrelin, is primarily expressed in the brain. Our previous study showed that neuronal GHSR deletion prevents high-fat diet-induced obesity (DIO). Here, we investigated the effect of neuronal GHSR deletion on emotional and cognitive functions in DIO. The neuron-specific GHSR-deficient mice exhibited reduced depression and improved spatial memory compared to littermate controls under DIO. We further examined the cortex and hippocampus, the major regions regulating cognitive and emotional behaviors, and found that the neuronal deletion of GHSR reduced DIO-induced neuroinflammation by suppressing proinflammatory chemokines/cytokines and decreasing microglial activation. Furthermore, our data showed that neuronal GHSR deletion suppresses neuroinflammation by downregulating AMPK-autophagy signaling in neurons. In conclusion, our data reveal that neuronal GHSR inhibition protects against DIO-induced depressive-like behavior and spatial cognitive dysfunction, at least in part, through AMPK-autophagy signaling-mediated neuroinflammation."

基金机构："NIH [P30 ES029067]; BrightFocus Foundation [A2019630S]; USDA Hatch project [7001445, Multistate 1022378]"

基金资助正文："The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by NIH 1R01DK118334, NIH AG064869 and BrightFocus Foundation Grant A2019630S (YS). This work was also supported in part by NIH P30 ES029067 (PI: David Threadgill), Institute for Advancing Health through Agriculture (PI: Patrick J. Stover), USDA Hatch project 7001445 and Multistate 1022378 (YS). The authors are also grateful to Michael R. Honig at Houston's Community Public Radio Station KPFT for his excellent editorial assistance."