Mice lacking the β2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia

Robin E. White, Curtis Palm, Lijun Xu, Evelyn Ling, Mitchell Ginsburg, Bernie J. Daigle, Ruquan Han, Andrew J Patterson, Russ B. Altman, Rona G. Giffard

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

The role of the β2AR (β2 adrenergic receptor) 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 with WT (wild-type) mice (FVB) after MCAO (middle cerebral artery occlusion), 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 deaths were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischaemia (Ccl9, Gem and Prg4). In addition to networks that were similar between genotypes, one network with a central core of GPCR (G-protein-coupled receptor) and including biological functions such as 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 both before and after ischaemia. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in β2KO mice in both sham and MCAO conditions. As both genes are implicated in NF-κB (nuclear factor κB) signalling, we measured p65 activity and TNFα (tumour necrosis factor α) levels 24 h after MCAO. MCAO-induced p65 activation and post-ischaemic TNFα production were both greater in FVB compared with β2KO mice. These results suggest that loss of β2AR signalling results in a neuroprotective phenotype in part due to decreased NF-κB signalling, decreased inflammation and decreased apoptotic signalling in the brain.

Original languageEnglish (US)
Pages (from-to)343-356
Number of pages14
JournalASN Neuro
Volume4
Issue number5
DOIs
StatePublished - Oct 1 2012

Fingerprint

Middle Cerebral Artery Infarction
Brain Ischemia
Adrenergic Receptors
Genotype
Inflammation
Genes
Ischemia
Tumor Necrosis Factor-alpha
Stroke
Noxae
Carbohydrate Metabolism
G-Protein-Coupled Receptors
Biochemistry
Cell Death
Pharmacology
Phenotype
Gene Expression
Messenger RNA
Brain
Proteins

Keywords

  • Glo1
  • Microarray
  • Noxa
  • Nuclear factor κB
  • Stroke
  • Tumour necrosis factor α
  • β2 adrenergic receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

Cite this

White, R. E., Palm, C., Xu, L., Ling, E., Ginsburg, M., Daigle, B. J., ... Giffard, R. G. (2012). Mice lacking the β2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia. ASN Neuro, 4(5), 343-356. https://doi.org/10.1042/AN20110020

Mice lacking the β2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia. / White, Robin E.; Palm, Curtis; Xu, Lijun; Ling, Evelyn; Ginsburg, Mitchell; Daigle, Bernie J.; Han, Ruquan; Patterson, Andrew J; Altman, Russ B.; Giffard, Rona G.

In: ASN Neuro, Vol. 4, No. 5, 01.10.2012, p. 343-356.

Research output: Contribution to journalArticle

White, RE, Palm, C, Xu, L, Ling, E, Ginsburg, M, Daigle, BJ, Han, R, Patterson, AJ, Altman, RB & Giffard, RG 2012, 'Mice lacking the β2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia', ASN Neuro, vol. 4, no. 5, pp. 343-356. https://doi.org/10.1042/AN20110020
White, Robin E. ; Palm, Curtis ; Xu, Lijun ; Ling, Evelyn ; Ginsburg, Mitchell ; Daigle, Bernie J. ; Han, Ruquan ; Patterson, Andrew J ; Altman, Russ B. ; Giffard, Rona G. / Mice lacking the β2 adrenergic receptor have a unique genetic profile before and after focal brain ischaemia. In: ASN Neuro. 2012 ; Vol. 4, No. 5. pp. 343-356.
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