Glycogen synthase kinase-3β is involved in electroacupuncture pretreatment via the cannabinoid CB1 receptor in ischemic stroke.
Mol Neurobiol. 2013-08-14; 49(1): 326-336
DOI: 10.1007/s12035-013-8524-5
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1. Mol Neurobiol. 2014 Feb;49(1):326-36. doi: 10.1007/s12035-013-8524-5. Epub 2013
Aug 14.
Glycogen synthase kinase-3β is involved in electroacupuncture pretreatment via
the cannabinoid CB1 receptor in ischemic stroke.
Wei H(1), Yao X, Yang L, Wang S, Guo F, Zhou H, Marsicano G, Wang Q, Xiong L.
Author information:
(1)Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical
University, Xi’an, 710032, Shaanxi, China.
We have previously shown that electroacupuncture (EA) pretreatment produces
neuroprotective effects, which were mediated through an endocannabinoid signal
transduction mechanism. Herein, we have studied the possible contribution of the
phosphorylated form of glycogen synthase kinase-3β (GSK-3β) in EA
pretreatment-induced neuroprotection via the cannabinoid CB1 receptor (CB1R).
Focal transient cerebral ischemia was induced by middle cerebral artery occlusion
in rats. Phosphorylation of GSK-3β at Ser-9 [p-GSK-3β (Ser-9)] was evaluated in
the penumbra tissue following reperfusion. Infarct size and neurological score
were assessed in the presence of either PI3K inhibitors or a GSK-3β inhibitor
72 h after reperfusion. Cellular apoptosis was evidenced by TUNEL staining and
determination of the Bax/Bcl-2 ratio 24 h after reperfusion. The present study
showed that EA pretreatment increased p-GSK-3β(Ser-9) 2 h after reperfusion in
the ipsilateral penumbra. Augmented phosphorylation of GSK-3β induced similar
neuroprotective effects as did EA pretreatment. By contrast, inhibition of PI3K
dampened the levels of p-GSK-3β(Ser-9), and reversed not only the neuroprotective
effect but also the anti-apoptotic effect following EA pretreatment. Regulation
of GSK-3β by EA pretreatment was abolished following treatment with a CB1R
antagonist and CB1R knockdown, whereas two CB1R agonists enhanced the
phosphorylation of GSK-3β. Therefore we conclude that EA pretreatment protects
against cerebral ischemia/reperfusion injury through CB1R-mediated
phosphorylation of GSK-3β.
DOI: 10.1007/s12035-013-8524-5
PMID: 23943518 [Indexed for MEDLINE]