Referenced in: none

Automatically associated channels: Nav1.5

Title: Dynamics of sodium channel Nav1.5 expression in astrocytes in mouse models of multiple sclerosis.

Authors: Laura W Pappalardo, Shujun Liu, Joel A Black, Stephen G Waxman

Journal, date & volume: Neuroreport, 2014 Oct 22 , 25, 1208-15

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25144393

Abstract
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.