Modulating Anxiety-Like Behaviors in Neuropathic Pain: Role of Anterior Cingulate Cortex Astrocytes Activation

IF 4.8 1区医学 Q1 NEUROSCIENCES CNS Neuroscience & Therapeutics Pub Date : 2025-01-21 DOI:10.1111/cns.70227

Qingqing Zhou, Qi Zhong, Zhuang Liu, Ziyue Zhao, Jie Wang, Zongze Zhang

{"title":"Modulating Anxiety-Like Behaviors in Neuropathic Pain: Role of Anterior Cingulate Cortex Astrocytes Activation","authors":"Qingqing Zhou, Qi Zhong, Zhuang Liu, Ziyue Zhao, Jie Wang, Zongze Zhang","doi":"10.1111/cns.70227","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>The comorbidity of anxiety-like symptoms in neuropathic pain (NP) is a significant yet often overlooked health concern. Anxiety sufferers may have a lower tolerance for pain, but which is difficult to treat. Accumulating evidence suggests a strong link between astrocytes and the manifestation of NP with concurrent anxiety-like behaviors. And the anterior cingulate cortex (ACC) has emerged as a key player in pain modulation and related emotional processing. However, the complex mechanisms that astrocytes in ACC influence anxiety behavior in mouse models of NP remain largely unexplored.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Utilizing the traditional spared nerve injury (SNI) surgical model, we employed chemogenetic approaches, immunofluorescence, and western blot to investigate the functional significance and interactive dynamics between ACC astrocytes and excitatory neurons.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Our results revealed that SNI surgery induces NP and delayed anxiety-like behaviors, accompanied by increased astrocyte activity in the ACC. Chemogenetic manipulation demonstrated that inhibiting astrocytes alleviates anxiety symptoms, while activating them exacerbates anxiety-like behaviors, affecting local excitatory neurons and synapse density. Direct manipulation of ACC excitatory neurons also significantly impacted anxiety-like behaviors.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our results highlight the pivotal role of ACC astrocytes in modulating anxiety-like behavior, suggesting a novel therapeutic strategy for anxiety associated with NP by targeting astrocyte function.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 1","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751476/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70227","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Aims

The comorbidity of anxiety-like symptoms in neuropathic pain (NP) is a significant yet often overlooked health concern. Anxiety sufferers may have a lower tolerance for pain, but which is difficult to treat. Accumulating evidence suggests a strong link between astrocytes and the manifestation of NP with concurrent anxiety-like behaviors. And the anterior cingulate cortex (ACC) has emerged as a key player in pain modulation and related emotional processing. However, the complex mechanisms that astrocytes in ACC influence anxiety behavior in mouse models of NP remain largely unexplored.

Methods

Utilizing the traditional spared nerve injury (SNI) surgical model, we employed chemogenetic approaches, immunofluorescence, and western blot to investigate the functional significance and interactive dynamics between ACC astrocytes and excitatory neurons.

Results

Our results revealed that SNI surgery induces NP and delayed anxiety-like behaviors, accompanied by increased astrocyte activity in the ACC. Chemogenetic manipulation demonstrated that inhibiting astrocytes alleviates anxiety symptoms, while activating them exacerbates anxiety-like behaviors, affecting local excitatory neurons and synapse density. Direct manipulation of ACC excitatory neurons also significantly impacted anxiety-like behaviors.

Conclusion

Our results highlight the pivotal role of ACC astrocytes in modulating anxiety-like behavior, suggesting a novel therapeutic strategy for anxiety associated with NP by targeting astrocyte function.

Abstract Image

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

神经性疼痛中焦虑样行为的调节：前扣带皮层星形胶质细胞激活的作用。

目的：神经性疼痛（NP）中焦虑样症状的共病是一个重要但经常被忽视的健康问题。焦虑患者可能对疼痛的耐受力较低，但这很难治疗。越来越多的证据表明星形胶质细胞与NP的表现与并发的焦虑样行为之间存在密切的联系。前扣带皮层（ACC）在疼痛调节和相关情绪处理中起着关键作用。然而，ACC中的星形胶质细胞影响NP小鼠焦虑行为的复杂机制在很大程度上仍未被探索。方法：利用传统的SNI手术模型，采用化学发生、免疫荧光、western blot等方法研究ACC星形胶质细胞与兴奋性神经元的功能意义及相互作用动力学。结果：我们的研究结果显示SNI手术诱导NP和延迟焦虑样行为，并伴有ACC中星形胶质细胞活性增加。化学发生操作表明，抑制星形胶质细胞可缓解焦虑症状，而激活它们会加剧焦虑样行为，影响局部兴奋性神经元和突触密度。直接操纵ACC兴奋性神经元也显著影响焦虑样行为。结论：我们的研究结果突出了ACC星形胶质细胞在调节焦虑样行为中的关键作用，为靶向星形胶质细胞功能治疗NP相关焦虑提供了一种新的治疗策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.