The GLP-1 receptor agonists exendin-4 and liraglutide alleviate oxidative stress and cognitive and micturition deficits induced by middle cerebral artery occlusion in diabetic mice

BMC Neuroscience

Research Article

Li-Fen Liu¹  Ming-Jia Jou¹  Hao-Kuang Wang²  Ping-Chia Li³ 

[1] School of Medicine for International Students, I-Shou University (Yanchao Campus), Kaohsiung, Taiwan;School of Medicine for International Students, I-Shou University (Yanchao Campus), Kaohsiung, Taiwan;Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan;School of Medicine for International Students, I-Shou University (Yanchao Campus), Kaohsiung, Taiwan;Department of Occupational Therapy, College of Medicine, I-Shou University (Yanchao Campus), Kaohsiung, Taiwan;

关键词: Cerebral microcirculation;    GLP-1 agonist;    Middle cerebral artery occlusion;    Oxidative stress;    Pelvic nerve;    Voiding function;   

DOI  :  10.1186/s12868-016-0272-9

 received in 2015-12-25, accepted in 2016-06-03,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundGlucagon-like peptide 1 (GLP-1) analogs protect a variety of cell types against oxidative damage and vascular and neuronal injury via binding to GLP-1 receptors. This study aimed to investigate the effects of the GLP-1 analogs exendin-4 and liraglutide on cerebral blood flow, reactive oxygen species production, expression of oxidative stress-related proteins, cognition, and pelvic sympathetic nerve-mediated bladder contraction after middle cerebral artery occlusion (MCAO) injury in the db/db mouse model of diabetes.ResultsSixty minutes of MCAO increased blood and brain reactive oxygen species counts in male db/db mice, as revealed by dihydroethidium staining. MCAO also increased nuclear factor-κB and intercellular adhesion molecule-1 expression and decreased cerebral microcirculation. These effects were attenuated by treatment with exendin-4 or liraglutide. MCAO did not affect basal levels of phosphorylated Akt (p-Akt) or endothelial nitric oxide synthase (p-eNOS); however, exendin-4 and liraglutide treatments significantly enhanced p-Akt and p-eNOS levels, indicating activation of the p-Akt/p-eNOS signaling pathway. MCAO-induced motor and cognitive deficits and micturition dysfunction, indicated by reduced pelvic nerve-mediated voiding contractions and increased nonvoiding contractions, were also partially attenuated by exendin-4 treatment.ConclusionsThe above data indicate that treatment with GLP-1 agonists exerts protective effects against oxidative, inflammatory, and apoptotic damage in brain areas that control parasympathetic/pelvic nerve-mediated voiding contractions and cognitive and motor behaviors in a diabetic mouse model.

【 授权许可】

CC BY   
© The Author(s) 2016