A single intracerebroventricular injection of LPS was administered into the lateral ventricle of a mouse and, 24 hours later, gene expression was examined in the cerebral cortex and hippocampus using microarray technology.? Gene set analysis showed that gene ontology (GO) terms for inflammation, cytokine activity, chemokine activity, and cytoskeletal reorganization, were significantly enriched 24 hours following the injection, whereas GO terms associated with nervous system development, neuron migration, synaptogenesis, and learning and memory showed decreased expression. Using strict criteria for individual genes, we detected 224 changed transcripts in the cortex and 170 in the hippocampus. Notably, expression of early growth response 1 (Egr1, also Zif268) and activity regulated cytoskeletal protein (Arc) mRNA were significantly lower in the cortex of LPS-treated animals. These effects are of interest because the protein products of Egr1 and Arc are induced during, and are required for, the consolidation of memory; reduced expression of these genes therefore may underlie some of the electrophysiological, behavioral, and cognitive changes observed in experimental neuroinflammation and in diseases with a marked neuroinflammatory component.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000149-01
Application #
7732147
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2008
Total Cost
$312,114
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code