Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

作     者：Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao Jie Tu Xirong Xu;Shoumin Xuan;Shuai Chen;Dan Liu;Qian Xiao;Jie Tu

作者机构：Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological DiseasesShenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina CAS Key Laboratory of Brain Connectome and ManipulationBrain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Brain Connectome and Behaviorthe Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese of Academy of SciencesBeijingChina Faculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2025年第20卷第6期

页      面：1721-1734页

核心收录：

学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX) the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL) the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT) the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX) Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT) Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT) the China Postdoctoral Science Foundation,No.2021M693298 (to QX) 

主　　题：anxiety astrocytes basolateral amygdala behavior dihydrokainic acid excitatory amino acid transporter 2 fiber photometry glutamate LDN-212320 transporter 

摘      要：The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with ***, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal *** knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was ob