RGD Reference Report - Role of glycogen synthase kinase 3 in ischemia-induced blood-brain barrier disruption in aged female rats. - Rat Genome Database
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Role of glycogen synthase kinase 3 in ischemia-induced blood-brain barrier disruption in aged female rats.

Authors: Xiao, Han  Deng, Mingyang  Yang, Binbin  Tang, Jianguang  Hu, Zhiping 
Citation: Xiao H, etal., J Neurochem. 2017 Jul;142(2):194-203. doi: 10.1111/jnc.14051. Epub 2017 May 26.
RGD ID: 13792734
Pubmed: (View Article at PubMed) PMID:28440874
DOI: Full-text: DOI:10.1111/jnc.14051

Estrogen receptors have protective effects against ischemic brain injury. However, the molecular mechanisms underlying this phenomenon have yet to be well studied. Given that inhibition of glycogen synthase kinase (GSK3) can reduce cerebral ischemia/reperfusion injury, we hypothesized that estrogen receptors-mediated protective effects against ischemia-induced blood-brain barrier (BBB) disruption involve inhibition of GSK3. Thus, we evaluated GSK3 expression in the brain of ovariectomized female rats, and examined the effects of intracerebroventricular pre-treatments of SB216763, GSK3 inhibitor, on BBB permeability following middle cerebral artery occlusion (MCAO). We also examined the role of specific estrogen receptor subtype in regulation of GSK3 expression and BBB permeability after MCAO. We found that ovariectomized female rats exhibited increased mRNA levels of estrogen receptor α (ERα) and estrogen receptor ß (ERß), and increased protein levels of GSK3ß but not GSK3α in brain cortical areas. Furthermore, intracerebroventricular pre-treatments of SB216763 dose-dependently attenuated brain infarction volume, brain water contents, neurological deficits, and BBB disruption, and increased tight junction protein ZO-1 and occludin expression at 24 h following MCAO. Finally, activation of ERß but not ERα dose-dependently decreased GSK3ß expression at 24 h following MCAO. This was associated with increased tight junction protein expression and improved neurological scores. Thus, our study suggested that activation of ERß may protect against brain ischemia-induced BBB disruption by inhibiting GSK3ß-mediated signaling.


Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Gsk3b  (glycogen synthase kinase 3 beta)

Genes (Mus musculus)
Gsk3b  (glycogen synthase kinase 3 beta)

Genes (Homo sapiens)
GSK3B  (glycogen synthase kinase 3 beta)

Additional Information