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Electroacupuncture Attenuates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice Through Adiponectin Receptor 1-Mediated Phosphorylation of GSK-3β

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Abstract

Diabetes mellitus substantially increases the risk of stroke and enhances brain’s vulnerability to ischemia insult. Electroacupuncture (EA) pretreatment was proved to induce cerebral ischemic tolerance in normal stroke models. Whether EA could attenuate cerebral ischemia injury in diabetic mice and the possible underlying mechanism are still unrevealed. Male C57BL/6 mice were subjected to streptozotocin (STZ) for diabetic models. After inducing focal cerebral ischemia model, the levels of plasma and cerebral adiponectin (APN) were measured as well as the expression of cerebral adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2). The neurobehavioral score, infarction volume, and cellular apoptosis were evaluated with or without AdipoR1 short interfering RNA (siRNA). The role of phosphorylation of glycogen synthesis kinase 3 beta (GSK-3β) at Ser-9 in the EA pretreatment was also assessed. EA pretreatment increased both plasma and cerebral APN levels and enhanced neuronal AdipoR1 in diabetic mice. In addition, EA reduced infarct size, improved neurological outcomes, and inhibited cell apoptosis after reperfusion. These beneficial effects were reversed by AdipoR1 knockdown. Furthermore, EA increased GSK-3β phosphorylation (p-GSK-3β) in the ipsilateral penumbra. Augmented p-GSK-3β induced neuroprotective effects similar to those of EA pretreatment. In contrast, dampened p-GSK-3β could reverse the neuroprotective effects of EA. In addition, the increase in p-GSK-3β by EA was abolished by AdipoR1 knockdown. We conclude that EA pretreatment increases the production of APN, which induce protective effects against cerebral ischemia-reperfusion injury through neuronal AdipoR1-mediated phosphorylation of GSK-3β in diabetic mice.

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Acknowledgments

This work was supported by the Overseas and Hong Kong, Macau Scholars Collaborated Researching Fund (Grant 81228022), the Program for Changjiang Scholars and Innovative Research Team in University (Grant IRT 1053), and the National Natural Science Foundation of China (Grants 81072888 and 81171278).

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The authors declare that they have no conflict of interest.

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Correspondence to Qiang Wang or Lize Xiong.

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Fan Guo and Tao Jiang contributed equally to this work

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Guo, F., Jiang, T., Song, W. et al. Electroacupuncture Attenuates Cerebral Ischemia-Reperfusion Injury in Diabetic Mice Through Adiponectin Receptor 1-Mediated Phosphorylation of GSK-3β. Mol Neurobiol 51, 685–695 (2015). https://doi.org/10.1007/s12035-014-8765-y

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