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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-11
pubmed:abstractText
We have developed an animal model of learning and memory impairment associated with activation of microglia in the mouse brain. Injection of lipopolysaccharide into the CA1 region of the mouse hippocampus resulted in an increased production of inflammatory cytokines, such as interleukin-1?. Immunostaining for interleukin-1? revealed an increase in the signal at 6 hr after lipopolysaccharide injection. Immunopositive cells for interleukin-1? were colocalized with those immunopositive for CD11b. When subacute lipopolysaccharide treatment (20 ?g/2 ?l/injection, bilaterally for 5 consecutive days) was performed, long-term activation of microglia and learning and memory deficits as evaluated using a step-through passive avoidance test were observed in the wild-type mice. Gene expression of the N-methyl-D-aspartate receptor NR1 and NR2A subunits was also decreased by the lipopolysaccharide treatment. In contrast, activation of microglia and the associated behavioral deficits were not observed in mice lacking interleukin-1? and -1? following the subacute lipopolysaccharide treatment, together with little change in the gene expression of NR1 and NR2A subunits. However, the subacute lipopolysaccharide treatment produced almost similar changes in those parameters in the tumor necrosis factor-? knockout mice as in the wild-type animals. The injection of interleukin-1? neutralizing antibody with lipopolysaccharide for 5 consecutive days resulted in the improvement of lipopolysaccharide-induced learning and memory deficits. These findings suggest that the expression of interleukin-1 plays an important role in lipopolysaccharide-induced activation of microglia and the associated functional deficits in learning and memory.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1097-4547
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
506-14
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Involvement of interleukin-1 in lipopolysaccaride-induced microglial activation and learning and memory deficits.
pubmed:affiliation
Department of Biochemical Toxicology, School of Pharmacy, Showa University, Tokyo, Japan. stanaka@pharm.showa-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't