{"title":"降低电压门控钠通道β 2的表达可恢复Aβ1-42诱导的神经元损伤和改善认知功能障碍。","authors":"Shan Li, Guo-Ji Yan, Ya-Xin Tan, Lu-Lu Xue, Ting-Hua Wang, Hao-Ran Zhao, Min-Nan Lu, Hui-Xiang Zhang, Rong Mei, Xiao-Han Dong, Li-Na Liu, Dan Wang, Yan-Bin Xiyang","doi":"10.1155/2022/3995227","DOIUrl":null,"url":null,"abstract":"<p><p>Voltage-gated sodium channel beta 2 (Nav2.2 or Nav<i>β</i>2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Nav<i>β</i>2 in amyloid-<i>β</i> 1-42- (A<i>β</i>1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Nav<i>β</i>2 knockdown restored neuronal viability of A<i>β</i>1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including A<i>β</i>42, sAPP<i>α</i>, and sAPP<i>β</i>, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating A<i>β</i> degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Nav<i>β</i>2 plays crucial roles in the repair of neuronal injury induced by A<i>β</i>1-42 both <i>in vivo</i> and <i>in vitro</i>.</p>","PeriodicalId":51299,"journal":{"name":"Neural Plasticity","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671742/pdf/","citationCount":"1","resultStr":"{\"title\":\"Reduced Expression of Voltage-Gated Sodium Channel Beta 2 Restores Neuronal Injury and Improves Cognitive Dysfunction Induced by A<i>β</i>1-42.\",\"authors\":\"Shan Li, Guo-Ji Yan, Ya-Xin Tan, Lu-Lu Xue, Ting-Hua Wang, Hao-Ran Zhao, Min-Nan Lu, Hui-Xiang Zhang, Rong Mei, Xiao-Han Dong, Li-Na Liu, Dan Wang, Yan-Bin Xiyang\",\"doi\":\"10.1155/2022/3995227\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Voltage-gated sodium channel beta 2 (Nav2.2 or Nav<i>β</i>2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Nav<i>β</i>2 in amyloid-<i>β</i> 1-42- (A<i>β</i>1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Nav<i>β</i>2 knockdown restored neuronal viability of A<i>β</i>1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including A<i>β</i>42, sAPP<i>α</i>, and sAPP<i>β</i>, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating A<i>β</i> degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Nav<i>β</i>2 plays crucial roles in the repair of neuronal injury induced by A<i>β</i>1-42 both <i>in vivo</i> and <i>in vitro</i>.</p>\",\"PeriodicalId\":51299,\"journal\":{\"name\":\"Neural Plasticity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9671742/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neural Plasticity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1155/2022/3995227\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neural Plasticity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2022/3995227","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 1
摘要
电压门控钠通道β2 (Nav2.2或Navβ2,由SCN2B mRNA编码)是一个参与维持前额叶皮层和海马正常生理功能的基因,可能与前额叶皮层老化和记忆衰退有关。本研究探讨了Navβ2在淀粉样蛋白-β 1-42- (a -β 1-42-)诱导的神经损伤模型中的作用及其可能的分子机制。结果表明,敲低Navβ2可恢复a β1-42损伤后的神经元活力;脑源性神经营养因子(BDNF)、NEP酶(NEP)蛋白含量和NEP酶活性均显著升高;并有效改变淀粉样前体蛋白(APP)代谢物(包括Aβ42、sAPPα和sAPPβ)的比例,从而改善认知功能障碍。这可能通过调节NEP转录和APP代谢,加速Aβ降解,减轻神经元损伤,调节bdnf相关信号通路来修复神经元突触效率来实现。本研究提供了新的证据,表明在体内和体外,Navβ2在a - β1-42诱导的神经元损伤的修复中起重要作用。
Reduced Expression of Voltage-Gated Sodium Channel Beta 2 Restores Neuronal Injury and Improves Cognitive Dysfunction Induced by Aβ1-42.
Voltage-gated sodium channel beta 2 (Nav2.2 or Navβ2, coded by SCN2B mRNA), a gene involved in maintaining normal physiological functions of the prefrontal cortex and hippocampus, might be associated with prefrontal cortex aging and memory decline. This study investigated the effects of Navβ2 in amyloid-β 1-42- (Aβ1-42-) induced neural injury model and the potential underlying molecular mechanism. The results showed that Navβ2 knockdown restored neuronal viability of Aβ1-42-induced injury in neurons; increased the contents of brain-derived neurotrophic factor (BDNF), enzyme neprilysin (NEP) protein, and NEP enzyme activity; and effectively altered the proportions of the amyloid precursor protein (APP) metabolites including Aβ42, sAPPα, and sAPPβ, thus ameliorating cognitive dysfunction. This may be achieved through regulating NEP transcription and APP metabolism, accelerating Aβ degradation, alleviating neuronal impairment, and regulating BDNF-related signal pathways to repair neuronal synaptic efficiency. This study provides novel evidence indicating that Navβ2 plays crucial roles in the repair of neuronal injury induced by Aβ1-42 both in vivo and in vitro.
期刊介绍:
Neural Plasticity is an international, interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology. Neural Plasticity publishes research and review articles from the entire range of relevant disciplines, including basic neuroscience, behavioral neuroscience, cognitive neuroscience, biological psychology, and biological psychiatry.