中国实用神经疾病杂志2024，Vol.27Issue(1)：1-8,8.DOI:10.12083/SYSJ.230146
前扣带回皮层中CaMKⅡα+GAD67+神经元在大鼠神经病理性疼痛和焦虑抑郁共病中的作用
Effect of CaMKⅡα+ and GAD67+ neurons in the anterior cingulate cortex in the co-morbidity of neuropathic pain and anxiety,depression in rats
摘要
Abstract
Objective To investigate the role of excitatory neurons expressing calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)and inhibitory neurons expressing glutamic acid decarboxylase 67(GAD67)in the anterior cingulate cortex(ACC)in neuropathic pain as well as anxiety and depression co-morbidity.Methods Seventy-two male SD rats were randomly divided into sham-operated group(Sham),neuropathic pain group(CCI),neuropathic pain + CaMKⅡα inactivation group(CCI+hM4Di-),neuropathic pain + CaMKⅡα activation group(CCI+ hM4Di+),neuropathic pain + GAD67 inactivation group(CCI+hM3Dq-),and neuropathic pain+GAD67 activation group(CCI+hM3Dq+).Neuronal activity was modulated in a cell-type and time-dependent manner by coupling hM3Dq or hM4Di via designer receptors(DREADDs)activated by a specifically designed drug technique.PWL and PWT were observed in each group of rats.Anxiety and depression-like behaviors were assessed in the absentee field assay,new environment feeding inhibition assay and forced swimming assay.The expressions of CaMKⅡα and GAD67 were detected by Western Blot.The neuronal activation was detected by immunofluorescence staining with c-Fos co-labeling.Results Compared with the Sham group,the CCI rats showed mechanical nociceptive hypersensitivity and thermal hyperalgesia,as well as anxiety and depression-like behaviors.The expression level of CaMKⅡα protein was increased and that of GAD67 protein was decreased in the contralateral ACC.Immunofluorescence staining showed increased activation of CaMKⅡα+ neurons and decreased activation of GAD67+ neurons.Compared with the CCI+hM4Di-group,the rats in the CCI+hM4Di+ group showed significantly higher PWL and PWT and improved anxiety and depression-like behaviors at 28-day.Compared with the CCI+hM3Dq-group,the CCI+hM3Dq+ group showed significantly higher PWL and PWT,and reduced anxiety and depression-like behaviors at 28-day.Conclusion Inhibition of CaMKⅡα+ excitatory neurons or activation of GAD67+ inhibitory neurons in ACC can reduce pain and improve anxiety and depression-like behavior in NP rats.关键词
神经病理性疼痛/焦虑/抑郁/由特定药物激活的受体/CaMKⅡα+神经元/GAD67+神经元/前扣带回皮层/大鼠Key words
Neuropathic pain/Anxiety/Depression/Designer receptors exclusively activated by designer drugs/CaMKⅡα+ neurons/GAD67+ neurons/Anterior cingulate cortex/Rats分类
医药卫生引用本文复制引用
王文婷,许耀威,白倩,李治松..前扣带回皮层中CaMKⅡα+GAD67+神经元在大鼠神经病理性疼痛和焦虑抑郁共病中的作用[J].中国实用神经疾病杂志,2024,27(1):1-8,8.基金项目
河南省医学科技攻关计划省部共建青年项目(编号:SBGJ2021030880) （编号:SBGJ2021030880）
河南省中青年卫生科技创新优秀青年人才培养项目(编号:YXKC2020059,YXKC2021018) （编号:YXKC2020059,YXKC2021018）
