Electroacupuncture attenuates cerebral ischemia-reperfusion injury in diabetic mice through adiponectin receptor 1-mediated phosphorylation of GSK-3β.

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.

• Authors: Fan Guo, Tao Jiang, Wenying Song, Haidong Wei, Feng Wang, Lixin Liu, Lei Ma, Hong Yin, Qiang Wang, Lize Xiong
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 51 Issue 2 Pg. 685-95 (Apr 2015) ISSN: 1559-1182 [Electronic] United States
• PMID: 24915968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Adiponectin
• adiponectin receptor 1, mouse
• Glycogen Synthase Kinase 3 beta
• Gsk3b protein, mouse
• Glycogen Synthase Kinase 3

Topics

• Animals
• Brain Ischemia (metabolism, prevention & control)
• Diabetes Mellitus, Experimental (metabolism, therapy)
• Electroacupuncture (methods)
• Glycogen Synthase Kinase 3 (metabolism)
• Glycogen Synthase Kinase 3 beta
• Male
• Mice
• Mice, Inbred C57BL
• Phosphorylation (physiology)
• Receptors, Adiponectin (physiology)
• Reperfusion Injury (metabolism, prevention & control)