文献类型：期刊文献

英文题名：GM1 Ameliorates Lead-Induced Cognitive Deficits and Brain Damage Through Activating the SIRT1/CREB/BDNF Pathway in the Developing Male Rat Hippocampus

作者：Chen, Fei[1,2,3];Zhou, Can-Can[1];Yang, Yin[1];Liu, Jian-Wen[2,3];Yan, Chong-Huai[1]

机构：[1]Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, MOE Shanghai Key Lab Childrens Environm Hlth, Shanghai 200092, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2019

卷号：190

期号：2

起止页码：425

外文期刊名：BIOLOGICAL TRACE ELEMENT RESEARCH

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000473414000016)】；

基金：This work was supported by the National Basic Research Program of China (973 Program, 2012CB525001), the National Natural Science Foundation of China (Grant No. 81472993), and National Key R&D Program of China (2017YFC1600500).

语种：英文

外文关键词：GM1; Lead; Neurotoxicity; Oxidative stress; Apoptosis; SIRT1

摘要：Developmental lead (Pb) exposure involves various serious consequences, especially leading to neurotoxicity. In this study, we examined the possible role of monosialoganglioside (GM1) in lead-induced nervous impairment in the developing rat. Newborn male Sprague-Dawley rat pups were exposed to lead from birth for 30days and then subjected to GM1 administration (0.4, 2, or 10mg/kg; i.p.) or 0.9% saline. The results showed that developmental lead exposure significantly impaired spatial learning and memory in the Morris water maze test, reduced GM1 content, induced oxidative stress, and weakened the antioxidative systems in the hippocampus. However, co-treatment with GM1 reversed these effects. Moreover, GM1 counteracted lead-induced apoptosis by decreasing the expression of Bax, cleaved caspase-3, and by increasing the level of Bcl-2 in a dose-dependent manner. Furthermore, we found that GM1 upregulated the expression of SIRT1, CREB phosphorylation, and BDNF, which underlie learning and memory in the lead-treated developing rat hippocampus. In conclusion, our study demonstrated that GM1 exerts a protective effect on lead-induced cognitive deficits via antioxidant activity, preventing apoptosis, and activating SIRT1/CREB/BDNF in the developing rat hippocampus, implying a novel potential assistant therapy for lead poisoning.