Helin Zou, Weiyu Pu, Junli Zhou, Juan Li, Lulin Ma, Shuxian Wang, Chengxi Liu, Jing Mou, Xingfeng Liu, Tian Yu, Yiyong Wei, Haihui Xie, Song Cao
{"title":"去肾上腺素能蓝斑ca3激活通过抑制SNI小鼠小胶质神经炎症减轻神经性疼痛和焦虑抑郁样行为","authors":"Helin Zou, Weiyu Pu, Junli Zhou, Juan Li, Lulin Ma, Shuxian Wang, Chengxi Liu, Jing Mou, Xingfeng Liu, Tian Yu, Yiyong Wei, Haihui Xie, Song Cao","doi":"10.1111/cns.70360","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Neuropathic pain (NP) arises from neuroimmune interactions following nerve injury and is often accompanied by anxiety and depression. The aim of the study is to evaluate the effects of the noradrenergic locus coeruleus (LC), a key regulator of pain and emotional states, projects extensively to the hippocampus.</p>\n </section>\n \n <section>\n \n <h3> Method</h3>\n \n <p>We investigated the effects of chronic NP on LC integrity and its projections to the hippocampal CA3 region in spared nerve injury (SNI) mice with behavioral tests, immunohistochemistry, neurochemical analyses, and Gq-DREADD.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Chronic NP induced LC neuronal loss, reduced hippocampal norepinephrine (NE) release, and triggered microglial activation and neuroinflammation in CA3. Selective activation of LC-CA3 noradrenergic neurons using Gq-DREADD chemogenetics alleviated NP and comorbid anxiety- and depression-like behaviors. This intervention suppressed microglial activation, decreased proinflammatory cytokines (TNF-α and IL-1β), and restored NE levels in CA3.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our findings highlighted the therapeutic potential of targeting LC-CA3 projections to mitigate chronic NP and its neuropsychiatric comorbidities via modulation of hippocampal neuroinflammation.</p>\n </section>\n </div>","PeriodicalId":154,"journal":{"name":"CNS Neuroscience & Therapeutics","volume":"31 3","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70360","citationCount":"0","resultStr":"{\"title\":\"Noradrenergic Locus Coeruleus-CA3 Activation Alleviates Neuropathic Pain and Anxiety- and Depression-Like Behaviors by Suppressing Microglial Neuroinflammation in SNI Mice\",\"authors\":\"Helin Zou, Weiyu Pu, Junli Zhou, Juan Li, Lulin Ma, Shuxian Wang, Chengxi Liu, Jing Mou, Xingfeng Liu, Tian Yu, Yiyong Wei, Haihui Xie, Song Cao\",\"doi\":\"10.1111/cns.70360\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>Neuropathic pain (NP) arises from neuroimmune interactions following nerve injury and is often accompanied by anxiety and depression. The aim of the study is to evaluate the effects of the noradrenergic locus coeruleus (LC), a key regulator of pain and emotional states, projects extensively to the hippocampus.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Method</h3>\\n \\n <p>We investigated the effects of chronic NP on LC integrity and its projections to the hippocampal CA3 region in spared nerve injury (SNI) mice with behavioral tests, immunohistochemistry, neurochemical analyses, and Gq-DREADD.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Chronic NP induced LC neuronal loss, reduced hippocampal norepinephrine (NE) release, and triggered microglial activation and neuroinflammation in CA3. Selective activation of LC-CA3 noradrenergic neurons using Gq-DREADD chemogenetics alleviated NP and comorbid anxiety- and depression-like behaviors. This intervention suppressed microglial activation, decreased proinflammatory cytokines (TNF-α and IL-1β), and restored NE levels in CA3.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Our findings highlighted the therapeutic potential of targeting LC-CA3 projections to mitigate chronic NP and its neuropsychiatric comorbidities via modulation of hippocampal neuroinflammation.</p>\\n </section>\\n </div>\",\"PeriodicalId\":154,\"journal\":{\"name\":\"CNS Neuroscience & Therapeutics\",\"volume\":\"31 3\",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-03-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cns.70360\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"CNS Neuroscience & Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cns.70360\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS Neuroscience & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cns.70360","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Noradrenergic Locus Coeruleus-CA3 Activation Alleviates Neuropathic Pain and Anxiety- and Depression-Like Behaviors by Suppressing Microglial Neuroinflammation in SNI Mice
Objective
Neuropathic pain (NP) arises from neuroimmune interactions following nerve injury and is often accompanied by anxiety and depression. The aim of the study is to evaluate the effects of the noradrenergic locus coeruleus (LC), a key regulator of pain and emotional states, projects extensively to the hippocampus.
Method
We investigated the effects of chronic NP on LC integrity and its projections to the hippocampal CA3 region in spared nerve injury (SNI) mice with behavioral tests, immunohistochemistry, neurochemical analyses, and Gq-DREADD.
Results
Chronic NP induced LC neuronal loss, reduced hippocampal norepinephrine (NE) release, and triggered microglial activation and neuroinflammation in CA3. Selective activation of LC-CA3 noradrenergic neurons using Gq-DREADD chemogenetics alleviated NP and comorbid anxiety- and depression-like behaviors. This intervention suppressed microglial activation, decreased proinflammatory cytokines (TNF-α and IL-1β), and restored NE levels in CA3.
Conclusion
Our findings highlighted the therapeutic potential of targeting LC-CA3 projections to mitigate chronic NP and its neuropsychiatric comorbidities via modulation of hippocampal neuroinflammation.
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.
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