Linked Life Data

15390090

Source:http://linkedlifedata.com/resource/pubmed/id/15390090

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-11-30
pubmed:abstractText
Loss of axons is a major contributor to nonremitting deficits in the inflammatory demyelinating disease multiple sclerosis (MS). Based on biophysical studies showing that activity of axonal sodium channels can trigger axonal degeneration, recent studies have tested sodium channel-blocking drugs in experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and have demonstrated a protective effect on axons. However, it is possible that, in addition to a direct effect on axons, sodium channel blockers may also interfere with inflammatory mechanisms. We therefore examined the novel hypothesis that sodium channels contribute to activation of microglia and macrophages in EAE and acute MS lesions. In this study, we demonstrate a robust increase of sodium channel Nav1.6 expression in activated microglia and macrophages in EAE and MS. We further demonstrate that treatment with the sodium channel blocker phenytoin ameliorates the inflammatory cell infiltrate in EAE by 75%. Supporting a role for sodium channels in microglial activation, we show that tetrodotoxin, a specific sodium channel blocker, reduces the phagocytic function of activated rat microglia by 40%. To further confirm a role of Nav1.6 in microglial activation, we examined the phagocytic capacity of microglia from med mice, which lack Nav1.6 channels, and show a 65% reduction in phagocytic capacity compared with microglia from wildtype mice. Our findings indicate that sodium channels are important for activation and phagocytosis of microglia and macrophages in EAE and MS and suggest that, in addition to a direct neuroprotective effect on axons, sodium channel blockade may ameliorate neuroinflammatory disorders via anti-inflammatory mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0894-1491
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
220-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15390090-Animals, pubmed-meshheading:15390090-Axons, pubmed-meshheading:15390090-Disease Models, Animal, pubmed-meshheading:15390090-Encephalomyelitis, Autoimmune, Experimental, pubmed-meshheading:15390090-Female, pubmed-meshheading:15390090-Gliosis, pubmed-meshheading:15390090-Macrophages, pubmed-meshheading:15390090-Male, pubmed-meshheading:15390090-Mice, pubmed-meshheading:15390090-Mice, Inbred C57BL, pubmed-meshheading:15390090-Microglia, pubmed-meshheading:15390090-Multiple Sclerosis, pubmed-meshheading:15390090-Nerve Degeneration, pubmed-meshheading:15390090-Nerve Tissue Proteins, pubmed-meshheading:15390090-Neuroprotective Agents, pubmed-meshheading:15390090-Phagocytosis, pubmed-meshheading:15390090-Phenytoin, pubmed-meshheading:15390090-RNA, Messenger, pubmed-meshheading:15390090-Sodium Channel Blockers, pubmed-meshheading:15390090-Sodium Channels, pubmed-meshheading:15390090-Tetrodotoxin, pubmed-meshheading:15390090-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
Sodium channels contribute to microglia/macrophage activation and function in EAE and MS.
pubmed:affiliation
Department of Neurology and Center for Neuroscience and Regeneration Research, Yale School of Medicine, New Haven, Connecticut 06520-8018, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't