{"title":"丘脑腹侧后外侧核中 Nav1.6 表达的上调有助于帕金森病模型中的痛觉亢进","authors":"Zhiwei Li, Jiamin Luo, Chengjiyuan Li, Hongyan Zhu","doi":"10.1016/j.expneurol.2024.115032","DOIUrl":null,"url":null,"abstract":"<div><div>Pain is the most common non-motor manifestation of Parkinson's disease (PD), affecting the quality of life for patients. Nav1.6 is the most abundant subtype of voltage-gated sodium channels (VGSCs) in the brain of adult mammals. Here we investigated the expression patterns of Nav1.6 in the ventral posterolateral (VPL) nucleus of the thalamus and its involvement in the development of hyperalgesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. The results showed a significant increase in Nav1.6 expression in reactive astrocytes of the ipsilateral VPL in 6-OHDA-lesioned rats at 4 weeks post-injection. Moreover, 6-OHDA-lesioned rats exhibited mechanical hyperalgesia, but did not display thermal hyperalgesia in the ipsilateral paw at the same time point. The down-regulation of Nav1.6 in the ipsilateral VPL can reduce mechanical hyperalgesia and improve sensorimotor impairments in 6-OHDA- lesioned rats. Furthermore, the analysis of local field potentials (LFPs) revealed that the increased Nav1.6 may participate in abnormal synchronized oscillations within the thalamocortical loop in 6-OHDA-lesioned rats. These findings suggest that the altered expression of Nav1.6 in astrocytes of the VPL may play an important role in the abnormal processing of pain within the thalamocortical circuit, contributing to the formation of mechanical hyperalgesia in animal models of PD.</div></div>","PeriodicalId":12246,"journal":{"name":"Experimental Neurology","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Upregulation of Nav1.6 expression in the ventral posterolateral nucleus of thalamus contributes to hyperalgesia in a model of Parkinson's disease\",\"authors\":\"Zhiwei Li, Jiamin Luo, Chengjiyuan Li, Hongyan Zhu\",\"doi\":\"10.1016/j.expneurol.2024.115032\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Pain is the most common non-motor manifestation of Parkinson's disease (PD), affecting the quality of life for patients. Nav1.6 is the most abundant subtype of voltage-gated sodium channels (VGSCs) in the brain of adult mammals. Here we investigated the expression patterns of Nav1.6 in the ventral posterolateral (VPL) nucleus of the thalamus and its involvement in the development of hyperalgesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. The results showed a significant increase in Nav1.6 expression in reactive astrocytes of the ipsilateral VPL in 6-OHDA-lesioned rats at 4 weeks post-injection. Moreover, 6-OHDA-lesioned rats exhibited mechanical hyperalgesia, but did not display thermal hyperalgesia in the ipsilateral paw at the same time point. The down-regulation of Nav1.6 in the ipsilateral VPL can reduce mechanical hyperalgesia and improve sensorimotor impairments in 6-OHDA- lesioned rats. Furthermore, the analysis of local field potentials (LFPs) revealed that the increased Nav1.6 may participate in abnormal synchronized oscillations within the thalamocortical loop in 6-OHDA-lesioned rats. These findings suggest that the altered expression of Nav1.6 in astrocytes of the VPL may play an important role in the abnormal processing of pain within the thalamocortical circuit, contributing to the formation of mechanical hyperalgesia in animal models of PD.</div></div>\",\"PeriodicalId\":12246,\"journal\":{\"name\":\"Experimental Neurology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Experimental Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0014488624003583\",\"RegionNum\":2,\"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":"Experimental Neurology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014488624003583","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Upregulation of Nav1.6 expression in the ventral posterolateral nucleus of thalamus contributes to hyperalgesia in a model of Parkinson's disease
Pain is the most common non-motor manifestation of Parkinson's disease (PD), affecting the quality of life for patients. Nav1.6 is the most abundant subtype of voltage-gated sodium channels (VGSCs) in the brain of adult mammals. Here we investigated the expression patterns of Nav1.6 in the ventral posterolateral (VPL) nucleus of the thalamus and its involvement in the development of hyperalgesia in 6-hydroxydopamine (6-OHDA)-lesioned rats. The results showed a significant increase in Nav1.6 expression in reactive astrocytes of the ipsilateral VPL in 6-OHDA-lesioned rats at 4 weeks post-injection. Moreover, 6-OHDA-lesioned rats exhibited mechanical hyperalgesia, but did not display thermal hyperalgesia in the ipsilateral paw at the same time point. The down-regulation of Nav1.6 in the ipsilateral VPL can reduce mechanical hyperalgesia and improve sensorimotor impairments in 6-OHDA- lesioned rats. Furthermore, the analysis of local field potentials (LFPs) revealed that the increased Nav1.6 may participate in abnormal synchronized oscillations within the thalamocortical loop in 6-OHDA-lesioned rats. These findings suggest that the altered expression of Nav1.6 in astrocytes of the VPL may play an important role in the abnormal processing of pain within the thalamocortical circuit, contributing to the formation of mechanical hyperalgesia in animal models of PD.
期刊介绍:
Experimental Neurology, a Journal of Neuroscience Research, publishes original research in neuroscience with a particular emphasis on novel findings in neural development, regeneration, plasticity and transplantation. The journal has focused on research concerning basic mechanisms underlying neurological disorders.