Adiponectin confers neuroprotection against cerebral ischemia-reperfusion injury through activating the cAMP/PKA-CREB-BDNF signaling.

Abstract

Ischemic stroke is a severe cerebrovascular disease. Although great progress has been made, the consequent ischemia-reperfusion (I/R) injury is inevitable and affects the therapeutic effect. Adiponectin (APN) is a fat-derived plasma protein that has beneficial actions on cardiovascular disorders. The present study aims to investigate the effect of APN on I/R injury and the potential underlying mechanisms. In step 1, APN were administered for three times (once every 8 h) 24 h before middle cerebral artery occlusion (MCAO). The results indicated that APN treatment reduced infarct volume, neurological deficits and brain water content after I/R injury. Meanwhile, APN was proved to increase the expression of cAMP, PKA, CREB, and BDNF. In step 2, mice were randomly assigned into the Vehicle + I/R, APN + I/R, PKA activator + I/R, PKA inhibitor + APN + I/R groups. PKA activator, PKA inhibitor, as well as APN were administered for three times before MCAO. The results indicated that PKA inhibitor downregulated the expressions of cAMP, PKA, CREB, and BDNF which subsequently weakened the protective effects of APN on cerebral I/R injury. In conclusion, our findings further suggest that APN exerts protective effect against cerebral I/R injury might through the cAMP/PKA-CREB-BDNF signaling pathway. APN is a novel candidate in the treatment of I/R diseases in the future.

• Authors: Hao Bai, Lei Zhao, Haixiao Liu, Hao Guo, Wei Guo, Longlong Zheng, Xunyuan Liu, Xun Wu, Jianing Luo, Xia Li, Li Gao, Dayun Feng, Yan Qu
• Journal: Brain research bulletin (Brain Res Bull) Vol. 143 Pg. 145-154 (10 2018) ISSN: 1873-2747 [Electronic] United States
• PMID: 30395885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Adiponectin
• Brain-Derived Neurotrophic Factor
• Creb1 protein, mouse
• Cyclic AMP Response Element-Binding Protein
• Cyclic AMP
• Cyclic AMP-Dependent Protein Kinases

Topics

• Adiponectin (pharmacology)
• Animals
• Brain Ischemia (drug therapy, metabolism)
• Brain-Derived Neurotrophic Factor (metabolism)
• Cyclic AMP (metabolism)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Cyclic AMP-Dependent Protein Kinases (metabolism)
• Down-Regulation (drug effects)
• Infarction, Middle Cerebral Artery (drug therapy, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Neuroprotection
• Reperfusion Injury (drug therapy, metabolism)
• Signal Transduction (drug effects)
• Stroke (metabolism)