Mice Lacking the β2 Adrenergic Receptor Have a Unique Genetic Profile Before and After Focal Brain Ischemia
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ABSTRACT: The role of the beta2 adrenergic receptor (β2AR) after stroke is unclear as pharmacological manipulations of the β2AR have produced contradictory results. We previously showed that mice deficient in the β2AR (β2KO) had smaller infarcts compared to wild-type mice (FVB) after middle cerebral artery occlusion (MCAO), a model of stroke. To elucidate mechanisms of this neuroprotection, we evaluated changes in gene expression using microarrays comparing differences before and after MCAO, and differences between genotypes. Genes associated with inflammation and cell death were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischemia (Ccl9, Gem, and Prg4). In addition to networks that were similar between genotypes, one network with a central node of G protein-coupled receptor and including biological functions carbohydrate metabolism, small molecule biochemistry and inflammation was identified in FVB mice but not in β2KO mice. Analysis of differences between genotypes revealed 11 genes differentially expressed by genotype in all conditions. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in β2KO mice. As both genes are implicated in NFκB signaling, we measured p65 activity and tumor necrosis factor alpha (TNFα) levels 24h after MCAO. MCAO-induced p65 activation and post-ischemic TNFα production were both greater in FVB compared to β2KO mice. These results suggest that loss of β2AR signaling results in a neuroprotective phenotype in part due to decreased NFκB signaling, decreased inflammation, and decreased apoptotic signaling in the brain.
ORGANISM(S): Mus musculus
PROVIDER: GSE30655 | GEO | 2014/07/14
SECONDARY ACCESSION(S): PRJNA144603
REPOSITORIES: GEO
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