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

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Abstract

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 30 days and then subjected to GM1 administration (0.4, 2, or 10 mg/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.

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Acknowledgements

Fei Chen especially wants to thank the support from his senior CanCan Zhou.

Funding

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).

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Authors and Affiliations

  1. MOE-Shanghai Key Laboratory of Children’s Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China

    Fei Chen, Can-Can Zhou, Yin Yang & Chong-Huai Yan

  2. State Key Laboratory of Bioreactor Engineering and Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, People’s Republic of China

    Fei Chen & Jian-Wen Liu

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  1. Fei Chen
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  2. Can-Can Zhou
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  3. Yin Yang
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Correspondence to Chong-Huai Yan.

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This study was carried out in strict accordance with the international standards of animal care guidelines, and the experiments were approved by Institutional Animal Care Committee at Shanghai Jiao tong University School of Medicine.

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Chen, F., Zhou, CC., Yang, Y. et al. GM1 Ameliorates Lead-Induced Cognitive Deficits and Brain Damage Through Activating the SIRT1/CREB/BDNF Pathway in the Developing Male Rat Hippocampus. Biol Trace Elem Res 190, 425–436 (2019). https://doi.org/10.1007/s12011-018-1569-6

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