Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Astrocytes actively participate in the response of the central nervous system to injury, including in multiple sclerosis. Astrocytes can play both beneficial and detrimental roles in response to neuroinflammation; however, in extreme cases, astrogliosis can result in the formation of a glial scar, which can impede the regeneration of injured neurons. Although astrocytes do not express the voltage-gated sodium channel Nav1.5 in the nonpathological human brain, they exhibit robust upregulation of Nav1.5 within acute and chronic multiple sclerosis lesions. Recent work has indicated that Nav1.5 contributes to the pathways that regulate glial scar formation in vitro through modulation of intracellular Ca levels. However, the temporal dynamics of astrocytic Nav1.5 channel expression in response to neuroinflammatory pathologies has not been investigated. We examined astrocytes from mice with monophasic and chronic-relapsing (CR) experimental autoimmune encephalomyelitis (EAE) by immunohistochemical analysis to determine whether Nav1.5 is expressed in these cells, and whether the expression correlates with the severity of disease and/or phases of relapse and remission. Our results demonstrate that Nav1.5 is upregulated in astrocytes in situ in a temporal manner that correlates with disease severity in both monophasic and CR EAE. Further, in CR EAE, Nav1.5 expression is upregulated during relapses and subsequently attenuated during periods of remission. These observations are consistent with the suggestion that Nav1.5 can play a role in the response of astrocytes to inflammatory pathologies in the central nervous system and suggest Nav1.5 may be a potential therapeutic target to modulate reactive astrogliosis in vivo.
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PMID:Dynamics of sodium channel Nav1.5 expression in astrocytes in mouse models of multiple sclerosis. 2514 93

Astrogliosis is a hallmark of neuroinflammatory disorders such as multiple sclerosis (MS). A detailed understanding of the underlying molecular mechanisms governing astrogliosis might facilitate the development of therapeutic targets. We investigated whether Nav1.5 expression in astrocytes plays a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We created a conditional knockout of Nav1.5 in astrocytes and determined whether this affects the clinical course of EAE, focal macrophage and T cell infiltration, and diffuse activation of astrocytes. We show that deletion of Nav1.5 from astrocytes leads to significantly worsened clinical outcomes in EAE, with increased inflammatory infiltrate in both early and late stages of disease, unexpectedly, in a sex-specific manner. Removal of Nav1.5 in astrocytes leads to increased inflammation in female mice with EAE, including increased astroglial response and infiltration of T cells and phagocytic monocytes. These cellular changes are consistent with more severe EAE clinical scores. Additionally, we found evidence suggesting possible dysregulation of the immune response-particularly with regard to infiltrating macrophages and activated microglia-in female Nav1.5 KO mice compared with WT littermate controls. Together, our results show that deletion of Nav1.5 from astrocytes leads to significantly worsened clinical outcomes in EAE, with increased inflammatory infiltrate in both early and late stages of disease, in a sex-specific manner.
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PMID:Nav1.5 in astrocytes plays a sex-specific role in clinical outcomes in a mouse model of multiple sclerosis. 3019 75