GM1 Ameliorates Neuronal Injury in Rats after Cerebral Ischemia and Reperfusion: Potential Contribution of Effects on SPTBN1-mediated Signaling

被引:0
作者
Shi, Yun-Wei [1 ,2 ]
Xu, Chun-Cheng [1 ]
Sun, Chun-Yan [3 ]
Liu, Jia-Xing [1 ]
Zhao, Shu-Yong [3 ]
Liu, Dong [2 ]
Fan, Xing-Juan [4 ]
Wang, Cai-Ping [1 ]
机构
[1] Nantong Univ, Key Lab Neuroregenerat Jiangsu & Minist Educ, Coinnovat Ctr Neuroregenerat, NMPA Key Lab Res & Evaluat Tissue Engn Technol Pr, Nantong 226001, Jiangsu, Peoples R China
[2] Nantong Univ, Sch Life Sci, Nantong Lab Dev & Dis, SeYuan Road 9, Nantong 226019, Jiangsu, Peoples R China
[3] Qilu Pharmaceut Co Ltd, Jinan 250104, Shandong, Peoples R China
[4] Nantong Univ, Affiliated Hosp, Dept Neurol, Xisi Road 20, Nantong 226001, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
neuroprotection; SPTBN1; GM1; stroke; ischemia; Juan Fan); GUILLAIN-BARRE-SYNDROME; LOCAL HEALTH DISTRICT; EXOGENOUS GANGLIOSIDES; HIPPOCAMPAL-NEURONS; FOCAL ISCHEMIA; IMPAIRMENT; EXPRESSION; PROTECTS; REGENERATION; RESPONSES;
D O I
10.1016/j.neuroscience.2024.05.031
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Monosialoganglioside GM1 (GM1) has long been used as a therapeutic agent for neurological diseases in the clinical treatment of ischemic stroke. However, the mechanism underlying the neuroprotective function of GM1 is still obscure until now. In this study, we investigated the effects of GM1 in ischemia and reperfusion (I/R) brain injury models. Middle cerebral artery occlusion and reperfusion (MCAO/R) rats were treated with GM1 (60 mg<middle dot>kg-1<middle dot>d-1, tail vein injection) for 2 weeks. The results showed that GM1 substantially attenuated the MCAO/R-induced neurological dysfunction and inhibited the inflammatory responses and cell apoptosis in ischemic parietal cortex. We further revealed that GM1 inhibited the activation of NF kappa B/MAPK signaling pathway induced by MCAO/R injury. To explore its underlying mechanism of the neuroprotective effect, transcriptome sequencing was introduced to screen the differentially expressed genes (DEGs). By function enrichment and PPI network analyses, Sptbn1 was identified as a node gene in the network regulated by GM1 treatment. In the MCAO/R model of rats and oxygen-glucose deprivation and reperfusion (OGD/R) model of primary culture of rat cortical neurons, we first found that SPTBN1 was involved in the attenuation of I/R induced neuronal injury after GM1 administration. In SPTBN1-knockdown SH-SY5Y cells, the treatment with GM1 (20 mu M) significantly increased SPTBN1 level. Moreover, OGD/R decreased SPTBN1 level in SPTBN1-overexpressed SHSY5Y cells. These results indicated that GM1 might achieve its potent neuroprotective effects by regulating inflammatory response, cell apoptosis, and cytomembrane and cytoskeleton signals through SPTBN1. Therefore, SPTBN1 may be a potential target for the treatment of ischemic stroke.
引用
收藏
页码:103 / 118
页数:16
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