Hepatic kynurenic acid mediates phosphorylation of Nogo-A in the medial prefrontal cortex to regulate chronic stress-induced anxiety-like behaviors in mice  

作　　者：Lan Yan Wen-jing Wang Tong Cheng Di-ran Yang Ya-jie Wang Yang-ze Wan Feng-zhen Yang Kwok-Fai So Li Zhang 

机构地区：[1]Key Laboratory of CNS Regeneration(Ministry of Education),Guangdong-Hong Kong-Macao Institute of CNS Regeneration,Jinan University,Guangzhou,510632,China [2]Department of Rehabilitation Sciences,Faculty of Health and Social Sciences,Hong Kong Polytechnic University,Hong Kong SAR,China [3]College of Life Science and Technology,Jinan University,Guangzhou,510632,China [4]State Key Laboratory of Brain and Cognitive Science,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,China [5]Neuroscience and Neurorehabilitation Institute,University of Health and Rehabilitation Sciences,Qingdao,266114,China [6]Center for Exercise and Brain Science,School of Psychology,Shanghai University of Sport,Shanghai,200438,China [7]The First Affiliated Hospital of Xinxiang Medical University,Xinxiang,453003,China

出　　处：《Acta Pharmacologica Sinica》2024年第10期2032-2044,共13页中国药理学报（英文版）

基　　金：funded by STI2030-Major Projects(2022ZD0207600)to LZ;National Key Research and Development Program of China(2020YFA0113600)to LZ;National Natural Science Foundation of China(U22A20301 to KFS,32070955 to LZ);Key Research and Development Plan of Ningxia(2022BEG01004)to KFS;Guangdong Basic and Applied Basic Research Foundation(2023B1515040015)to LZ.

摘　　要：Exercise training effectively relieves anxiety disorders via modulating specific brain networks.The role of post-translational modification of proteins in this process,however,has been underappreciated.Here we performed a mouse study in which chronic restraint stress-induced anxiety-like behaviors can be attenuated by 14-day persistent treadmill exercise,in association with dramatic changes of protein phosphorylation patterns in the medial prefrontal cortex(mPFC).In particular,exercise was proposed to modulate the phosphorylation of Nogo-A protein,which drives the ras homolog family member A(RhoA)/Rho-associated coiled-coil-containing protein kinases 1(ROCK1)signaling cascade.Further mechanistic studies found that liver-derived kynurenic acid(KYNA)can affect the kynurenine metabolism within the mPFC,to modulate this RhoA/ROCK1 pathway for conferring stress resilience.In sum,we proposed that circulating KYNA might mediate stress-induced anxiety-like behaviors via protein phosphorylation modification within the mPFC,and these findings shed more insights for the liver-brain communications in responding to both stress and physical exercise.

关 键 词：protein phosphorylation kynurenic acid treadmill exercise medial prefrontal cortex anxiety disorders 

分 类 号：R749[医药卫生—神经病学与精神病学]