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

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外文摘要：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 emotions.Specifically,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 2 agonists 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 mice.After 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 obviously mitigated.Additionally,administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress.These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons,and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.

外文关键词：

anxietyastrocytesbasolateral amygdalabehaviordihydrokainic acidexcitatory amino acid transporter 2fiber photometryglutamateLDN-212320transporter

作者：

Xirong Xu、Shoumin Xuan、Shuai Chen、Dan Liu、Qian Xiao、Jie Tu

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作者单位：

Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,Shenzhen-Hong Kong Institute of Brain Science,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong Province,China

CAS Key Laboratory of Brain Connectome and Manipulation,Brain Cognition and Brain Disease Institute(BCBDI),Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong Province,China

Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,the Bra

Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,the Brain Cognition and Brain Disease Institute(BCBDI),Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,Guangdong Province,China

University of Chinese of Academy of Sciences,Beijing,China

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出版年：

2025

DOI：

10.4103/NRR.NRR-D-23-01411

中国神经再生研究(英文版)

中国康复医学会

中国神经再生研究(英文版)

影响因子：0.902

ISSN：1673-5374

年,卷(期)：2025.20(6)