利拉鲁肽
神经保护
莫里斯水上航行任务
内分泌学
链脲佐菌素
内科学
医学
海马体
认知功能衰退
海马结构
糖尿病
蛋白激酶B
药理学
生物
细胞凋亡
2型糖尿病
痴呆
生物化学
疾病
作者
Wenhui Yan,Pang Miao,Ye Yu,Xilan Gou,Peiru Si,Alina Zhawatibai,Yutong Zhang,Meng Zhang,Tingli Guo,Xinyao Yi,Lina Chen
出处
期刊:Life Sciences
[Elsevier]
日期:2019-06-12
卷期号:231: 116566-116566
被引量:52
标识
DOI:10.1016/j.lfs.2019.116566
摘要
Diabetes mellitus can cause cognitive impairments, a state between normal aging and dementia. Effective clinical interventions are urgently needed to prevent or treat this complication. Liraglutide as a glucagon-like peptide 1 analog has been shown to exert memory-enhancing and neuroprotective effects on neurodegenerative diseases. This study aims to investigate the neuroprotective effects of liraglutide in streptozotocin (STZ)-induced diabetic mice with cognitive deficits.Male C57BL/6J mice were intraperitoneal injected with STZ (65 mg/kg body weight daily for 5 days) to induce type 1 diabetes model. Then the mice were treated with liraglutide (250 mg/kg/day, for 6 weeks) or saline. Weekly changes of body weight and fasting blood glucose were measured. Cognitive performance was evaluated by Morris water maze test. The ultrastructure of hippocampus was observed by transmission electron microscope. The superoxide dismutase activities and malondialdehyde levels in the hippocampus were detected by biochemistry assay. Apoptosis-related proteins and phosphoinositide 3-kinase (PI3K)/protein kinase-B (Akt) signaling were detected by Western blotting.We found that STZ-induced diabetic mice exhibited impaired learning and memory, ultrastructure damage of hippocampal neurons and synapses, exacerbated oxidative stress and neuronal apoptosis, as compared to the control mice. These effects were attenuated by the treatment with liraglutide. Furthermore, liraglutide reversed diabetes-induced alterations in PI3K/Akt signaling pathway that plays an essential role in modulating neuronal survival, apoptosis and plasticity.These data suggest that the neuroprotective effects of liraglutide on diabetes-induced cognitive impairments are associated with the improvements of hippocampal synapses and inhibition of neuronal apoptosis.
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