TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is characterized by demyelination, axonal injury and neurological deterioration. Few medications are available for progressive MS, which is associated with neuroinflammation confined to the CNS compartment. Transient recep...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yu Shao, Chen Chen, Tao Zhu, Zengxian Sun, Shufen Li, Lifen Gong, Xinyan Dong, Weida Shen, Linghui Zeng, Yicheng Xie, Peifang Jiang
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Multiple sclerosis TRPM2 channel Neuroinflammation Cognitive dysfunction NLRP3 inflammasome Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/89eb03370a3d4e94bc1d493d08c73f5a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:89eb03370a3d4e94bc1d493d08c73f5a
record_format	dspace
spelling	oai:doaj.org-article:89eb03370a3d4e94bc1d493d08c73f5a2021-11-12T04:26:26ZTRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome1095-953X10.1016/j.nbd.2021.105534https://doaj.org/article/89eb03370a3d4e94bc1d493d08c73f5a2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0969996121002837https://doaj.org/toc/1095-953XMultiple sclerosis (MS) is a disease of the central nervous system (CNS) that is characterized by demyelination, axonal injury and neurological deterioration. Few medications are available for progressive MS, which is associated with neuroinflammation confined to the CNS compartment. Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that plays pathological roles in a wide range of neuroinflammatory diseases; however, the underlying molecular mechanisms of TRPM2 remain elusive. Here, we established a cuprizone model that presents hallmark MS pathologies to investigate the role of TRPM2 in progressive MS. We demonstrated that genetic deletion of TRPM2 yields protection from the cuprizone-induced demyelination, synapse loss, microglial activation, NLRP3 inflammasome activation and proinflammatory cytokines production and ultimately leads to an improvement in cognitive decline. Furthermore, we showed that the pharmacological inhibition of NLRP3 ameliorated the demyelination, neuroinflammation and cognitive impairment in the model with no additive effects on the TRPM2 KO mice. Taken together, these results indicated that TRPM2 plays important roles in regulating neuroinflammation in progressive MS via NLRP3 inflammasome, and the results shed light on TRPM2's potential role as a therapeutic target for MS.Yu ShaoChen ChenTao ZhuZengxian SunShufen LiLifen GongXinyan DongWeida ShenLinghui ZengYicheng XiePeifang JiangElsevierarticleMultiple sclerosisTRPM2 channelNeuroinflammationCognitive dysfunctionNLRP3 inflammasomeNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENNeurobiology of Disease, Vol 160, Iss , Pp 105534- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Multiple sclerosis TRPM2 channel Neuroinflammation Cognitive dysfunction NLRP3 inflammasome Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Multiple sclerosis TRPM2 channel Neuroinflammation Cognitive dysfunction NLRP3 inflammasome Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Yu Shao Chen Chen Tao Zhu Zengxian Sun Shufen Li Lifen Gong Xinyan Dong Weida Shen Linghui Zeng Yicheng Xie Peifang Jiang TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome
description	Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that is characterized by demyelination, axonal injury and neurological deterioration. Few medications are available for progressive MS, which is associated with neuroinflammation confined to the CNS compartment. Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that plays pathological roles in a wide range of neuroinflammatory diseases; however, the underlying molecular mechanisms of TRPM2 remain elusive. Here, we established a cuprizone model that presents hallmark MS pathologies to investigate the role of TRPM2 in progressive MS. We demonstrated that genetic deletion of TRPM2 yields protection from the cuprizone-induced demyelination, synapse loss, microglial activation, NLRP3 inflammasome activation and proinflammatory cytokines production and ultimately leads to an improvement in cognitive decline. Furthermore, we showed that the pharmacological inhibition of NLRP3 ameliorated the demyelination, neuroinflammation and cognitive impairment in the model with no additive effects on the TRPM2 KO mice. Taken together, these results indicated that TRPM2 plays important roles in regulating neuroinflammation in progressive MS via NLRP3 inflammasome, and the results shed light on TRPM2's potential role as a therapeutic target for MS.
format	article
author	Yu Shao Chen Chen Tao Zhu Zengxian Sun Shufen Li Lifen Gong Xinyan Dong Weida Shen Linghui Zeng Yicheng Xie Peifang Jiang
author_facet	Yu Shao Chen Chen Tao Zhu Zengxian Sun Shufen Li Lifen Gong Xinyan Dong Weida Shen Linghui Zeng Yicheng Xie Peifang Jiang
author_sort	Yu Shao
title	TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome
title_short	TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome
title_full	TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome
title_fullStr	TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome
title_full_unstemmed	TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome
title_sort	trpm2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via nlrp3 inflammasome
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/89eb03370a3d4e94bc1d493d08c73f5a
work_keys_str_mv	AT yushao trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT chenchen trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT taozhu trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT zengxiansun trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT shufenli trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT lifengong trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT xinyandong trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT weidashen trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT linghuizeng trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT yichengxie trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome AT peifangjiang trpm2contributestoneuroinflammationandcognitivedeficitsinacuprizoneinducedmultiplesclerosismodelvianlrp3inflammasome
_version_	1718431302726713344

TRPM2 contributes to neuroinflammation and cognitive deficits in a cuprizone-induced multiple sclerosis model via NLRP3 inflammasome

Ejemplares similares