实验性自身免疫性脑脊髓炎
赛马鲁肽
再髓鞘化
神经保护
医学
多发性硬化
兴奋剂
神经炎症
PI3K/AKT/mTOR通路
中枢神经系统
神经科学
免疫学
药理学
内分泌学
内科学
受体
生物
炎症
利拉鲁肽
信号转导
糖尿病
2型糖尿病
髓鞘
细胞生物学
作者
Mohamed A Sadek,Esraa A. Kandil,Nesrine S. El Sayed,Helmy M. Sayed,Mostafa A. Rabie
标识
DOI:10.1016/j.intimp.2022.109647
摘要
Multiple sclerosis (MS) is a disabling neurodegenerative disease that causes demyelination and axonal degeneration of the central nervous system. Current treatments are partially effective in managing MS relapses and have a negligible impact on treating MS cognitive deficits and cannot enhance neuronal remyelination, imposing a need for a new MS remedy. Semaglutide, a novel glucagon-like peptide-1 agonist, has recently displayed a neuroprotective effect on several neurodegenerative diseases, suggesting that it may have a protective effect in MS. Therefore, this study was conducted to investigate the influence of semaglutide on experimental autoimmune encephalomyelitis (EAE)-induced MS in mice. Here, EAE was induced in mice using spinal cord homogenate, which eventually altered the mice's cognitive and motor functions, similar to what is observed in MS. Interestingly, intraperitoneally administered semaglutide (25 nmol/kg/day) amended EAE-induced cognitive and motor deficits observed in novel object recognition, open field, rotarod, and grip strength tests. Moreover, histological examination revealed that semaglutide treatment attenuated hippocampal damage and corpus callosum demyelination caused by EAE. Additionally, biochemical testing revealed that semaglutide activates the PI3K/Akt axis, which eventually hampers GSK-3β activity. GSK-3β activity inhibition attenuates demyelination and triggers remyelination through CREB/BDNF; furthermore, it boosts Nrf2 and SOD levels, protecting the mice from EAE-induced oxidative stress. Additionally, GSK-3β inhibition minimizes neuroinflammation, as reflected by decreased NF-kβ and TNF-α levels. In conclusion, semaglutide has a neuroprotective effect in EAE-induced MS in mice, which is mediated by activating the ramified PI3K/Akt/GSK-3β pathway.
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