Neuropeptide-mediated activation of astrocytes improves stress resilience in mice by modulating cortical neural synapses  

作　　者：Jing Cui Xiao-ran Wang Jie Yu Bo-rui Zhang Ya-fei Shi Kwok-Fai So Li Zhang Ji-an Wei 

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

出　　处：《Acta Pharmacologica Sinica》2025年第4期867-879,共13页中国药理学报(英文版)

基　　金：funded by STI2030-Major Projects(2022ZD0207600)to LZ;National Natural Science Foundation of China(U22A20301 to KFS);Guangdong Major Project of Basic and Applied Basic Research(2023B0303000004)to KFS and LZ;Guangdong Basic and Applied Basic Research Foundation(2023B1515040015)to LZ;Guangdong Special Support Program for Young Talented Researchers(2023TQ07A102)to LZ;Guangzhou Basic and Applied Basic Research Foundation(SL2023A03J00544,SL2024A04J00149)to LZ;The Fundamental Research Funds for the Central Universities(21624207)to LZ;the Key Research and Development Plan of Ningxia(2022BEG01004)to KFS.

摘　　要：Astrocytes are known to modulate synaptogenesis or neuronal activities,thus participating in mental functions.It has been shown that astrocytes are involved in the antidepressant mechanism.In this study we investigated the potential hormonal mediator governing the astrocyte-neuron interplay for stress-coping behaviors.Mice were subjected to chronic restraint stress(CRS)for 14 days,and then brain tissue was harvested for analyses.We found that the expression of pituitary adenylate cyclase activating polypeptide(PACAP)and its receptor PAC1 was significantly decreased in astrocytes of the prelimbic(PrL)cortex.By conducting a combination of genetics,in vivo imaging and behavioral assays we demonstrated that PAC1 in cortical astrocytes was necessary for maintaining normal resilience of mice against chronic environmental stress like restraint stress.Furthermore,we showed the enhancement of de novo cortical spine formation and synaptic activity under PACAP-mediated astrocytic activation possibly via the ATP release.The molecular mechanisms suggested that the vesicle homeostasis mediated by PACAP-PAC1 axis in astrocytes was involved in regulating synaptic functions.This study identifies a previously unrecognized route by which neuropeptide modulates cortical functions via local regulation of astrocytes.

关 键 词：stress resilience astrocyte-neuron interplay NEUROPEPTIDE PACAP PAC1 SNARE pathway 

分 类 号：R338[医药卫生—人体生理学]