In:
European Journal of Neuroscience, Wiley, Vol. 49, No. 10 ( 2019-05), p. 1233-1243
Abstract:
Acid‐sensing ion channels ( ASIC s) are proton‐gated channels involved in multiple biological functions such as: pain modulation, mechanosensation, neurotransmission, and neurodegeneration. Earlier, we described the genetic association, within the Nuoro population, between Multiple Sclerosis ( MS ) and rs28936, located in ASIC 2 3′ UTR . Here we investigated the potential involvement of ASIC 2 in MS inflammatory process. We induced experimental autoimmune encephalomyelitis ( EAE ) in wild‐type ( WT ), knockout Asic1 −/− and Asic2 −/− mice and observed a significant reduction of clinical score in Asic1 −/− mice and a significant reduction in the clinical score in Asic2 −/− mice in a limited time window (i.e., at days 20–23 after immunization). Immunohistochemistry confirmed the reduction in adaptive immune cell infiltrates in the spinal cord of EAE Asic1 −/− mice. Analysis of mechanical allodynia, showed a significant higher pain threshold in Asic2 −/− mice under physiological conditions, before immunization, as compared to WT mice and Asic1 −/− . A significant reduction in pain threshold was observed in all three strains of mice after immunization. More importantly, analysis of human autoptic brain tissue in MS and control samples showed an increase of ASIC 2 mRNA in MS samples. Subsequently, in vitro luciferase reporter gene assays, showed that ASIC 2 expression is under possible mi RNA regulation, in a rs28936 allele‐specific manner. Taken together, these findings suggest a potential role of ASIC 2 in the pathophysiology of MS .
Type of Medium:
Online Resource
ISSN:
0953-816X
,
1460-9568
DOI:
10.1111/ejn.2019.49.issue-10
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2005178-5
SSG:
12
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