Involvement of GluR2 up-regulation in neuroprotection by electroacupuncture pretreatment via cannabinoid CB1 receptor in mice.

Zhaoyu Liu,Yang Gao,Qiang Wang,Qianzi Yang,Lei Yang,Fuhai Bai,Sisi Sun,Xiyao Chen,Lize Xiong

doi:10.1038/srep09490

Zhaoyu Liu, Yang Gao + Show 7 more

Open Access

https://doi.org/10.1038/srep09490

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Journal: Scientific Reports	Publication Date: Apr 1, 2015
Citations: 40	License type: CC BY 4.0

Affiliation: Air Force Medical University, Xijing Hospital

Abstract

We investigated whether glutamate receptor subunit 2 (GluR2) is involved in EA pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after global cerebral ischemia in mice. Two hours after electric acupuncture (EA) pretreatment, global cerebral ischemia (GCI) was induced by bilateral common carotid artery occlusion (BCCAO) for 20 min. The GluR2 expression was examined in the hippocampus after reperfusion. Cell survival, neuronal apoptosis, the Bax/Bcl-2 ratio and neurological scores were evaluated at 24 h after BCCAO in the presence or absence of the GluR2 inhibitor. Furthermore, the GluR2 was determined in the presence and absence of CB1R inhibitor. Our results showed EA pretreatment enhanced expression of GluR2 in the hippocampus 2 h after reperfusion. Moreover, EA pretreatment improved neurological outcome, promoted cell survival, inhibited neuronal apoptosis, and decreased the Bax/Bcl-2 ratio after reperfusion. GluR2 knockdown by GluR2 siRNA effectively reversed the beneficial effects of EA pretreatment. Furthermore, CB1R siRNA and two CB1R antagonists blocked the elevation of GluR2 expression by EA pretreatment, whereas the two CB1R agonists up-regulated GluR2 expression as EA pretreatment. In conclusion, GluR2 up-regulation is involved in neuroprotection of EA pretreatment against GCI through CB1R, suggesting that GluR2 may be a novel target for stroke intervention.

Highlights

We investigated whether glutamate receptor subunit 2 (GluR2) is involved in electric acupuncture (EA) pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after global cerebral ischemia in mice
EA pretreatment 2 h prior to global cerebral ischemia resulted in GluR2 up-regulation according to western blotting, and double-labeled immunolabeling
The analysis indicated pretreatment with EA significantly increased GluR2 protain in the hippocampus compared to the global cerebral ischemia (GCI) group (P 5 0.020; Fig. 2a)

Summary

Introduction

We investigated whether glutamate receptor subunit 2 (GluR2) is involved in EA pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after global cerebral ischemia in mice. Medical researchers wish to intervene and reduce this injury, but there are few effective pharmacological treatments once an ischemic stroke occurs Thrombolytics, such as Activase and TNKase, have been a significant advance, but these must be administered within 3–4.5 h of ischemia’s onset. Subsequent studies support a more central role for AMPA-type glutamate receptors in the selective pattern of neuronal loss in the hippocampus, which is associated with global ischemia[6]. Many neuroprotective drugs are designed to inhibit ischemia-induced excitotoxicity by acting as glutamate receptor antagonists. A rise in intracellular Ca21 may spur events leading to cell death, suggesting GluR2-lacking AMPAR-mediated excitotoxicity plays a critical role in cerebral ischemic insults[11].

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