Linked Life Data

20971854

Source:http://linkedlifedata.com/resource/pubmed/id/20971854

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-1-31
pubmed:abstractText
Neuroinflammation and associated neuronal dysfunction mediated by activated microglia play an important role in the pathogenesis of Alzheimer disease (AD). Microglia are activated by aggregated forms of amyloid-? protein (A?), usually demonstrated in vitro by stimulating microglia with micromolar concentrations of fibrillar A?, a major component of amyloid plaques in AD brains. Here we report that amyloid-? oligomer (A?O), at 5-50 nm, induces a unique pattern of microglia activation that requires the activity of the scavenger receptor A and the Ca(2+)-activated potassium channel KCa3.1. A?O treatment induced an activated morphological and biochemical profile of microglia, including activation of p38 MAPK and nuclear factor ?B. Interestingly, although increasing nitric oxide (NO) production, A?O did not increase several proinflammatory mediators commonly induced by lipopolyliposaccharides or fibrillar A?, suggesting that A?O stimulates both common and divergent pathways of microglia activation. A?O at low nanomolar concentrations, although not neurotoxic, induced indirect, microglia-mediated damage to neurons in dissociated cultures and in organotypic hippocampal slices. The indirect neurotoxicity was prevented by (i) doxycycline, an inhibitor of microglia activation; (ii) TRAM-34, a selective KCa3.1 blocker; and (iii) two inhibitors of inducible NO synthase, indicating that KCa3.1 activity and excessive NO release are required for A?O-induced microglial neurotoxicity. Our results suggest that A?O, generally considered a neurotoxin, may more potently cause neuronal damage indirectly by activating microglia in AD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
4
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3693-706
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity.
pubmed:affiliation
Medical Investigation of Neurodevelopmental Disorders Institute, University of California, Davis, California 95618, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural