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

Autor: Yan L; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China., Wang WJ; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China., Cheng T; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China.; Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong SAR, China., Yang DR; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China., Wang YJ; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China., Wang YZ; College of Life Science and Technology, Jinan University, Guangzhou, 510632, China., Yang FZ; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China., So KF; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China. hrmaskf@hku.hk.; State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. hrmaskf@hku.hk.; Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao, 266114, China. hrmaskf@hku.hk.; Center for Exercise and Brain Science, School of Psychology, Shanghai University of Sport, Shanghai, 200438, China. hrmaskf@hku.hk.; The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, China. hrmaskf@hku.hk., Zhang L; Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, 510632, China. zhangli@jnu.edu.cn.; Neuroscience and Neurorehabilitation Institute, University of Health and Rehabilitation Sciences, Qingdao, 266114, China. zhangli@jnu.edu.cn.; Center for Exercise and Brain Science, School of Psychology, Shanghai University of Sport, Shanghai, 200438, China. zhangli@jnu.edu.cn.; The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, China. zhangli@jnu.edu.cn.
Jazyk: angličtina
Zdroj: Acta pharmacologica Sinica [Acta Pharmacol Sin] 2024 Oct; Vol. 45 (10), pp. 2032-2044. Date of Electronic Publication: 2024 May 29.
DOI: 10.1038/s41401-024-01302-y
Abstrakt: 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.
(© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)
Databáze: MEDLINE
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