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The role of α-synuclein and tau hyperphosphorylation-mediated autophagy and apoptosis in lead-induced learning and memory injury.

Abstract

Lead (Pb) is a well-known heavy metal in nature. Pb can cause pathophysiological changes in several organ systems including central nervous system. Especially, Pb can affect intelligence development and the ability of learning and memory of children. However, the toxic effects and mechanisms of Pb on learning and memory are still unclear. To clarify the mechanisms of Pb-induced neurotoxicity in hippocampus, and its effect on learning and memory, we chose Sprague-Dawley rats (SD-rats) as experimental subjects. We used Morris water maze to verify the ability of learning and memory after Pb treatment. We used immunohistofluorescence and Western blotting to detect the level of tau phosphorylation, accumulation of α-synuclein, autophagy and related signaling molecules in hippocampus. We demonstrated that Pb can cause abnormally hyperphosphorylation of tau and accumulation of α-synuclein, and these can induce hippocampal injury and the ability of learning and memory damage. To provide the new insight into the underlying mechanisms, we showed that Grp78, ATF4, caspase-3, autophagy-related proteins were induced and highly expressed following Pb-exposure. But mTOR signaling pathway was suppressed in Pb-exposed groups. Our results showed that Pb could cause hyperphosphorylation of tau and accumulation of α-synuclein, which could induce ER stress and suppress mTOR signal pathway. These can enhance type II program death (autophgy) and type I program death (apoptosis) in hippocampus, and impair the ability of learning and memory of rats. This is the first evidence showing the novel role of autophagy in the neurotoxicity of Pb.

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    • Authors

    Zhang J, Cai T, Zhao F, Yao T, Chen Y, Liu X, Luo W, Chen J

    Institution

    Department of Occupational & Environmental Health and Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, 710032, China.

    Source

    International journal of biological sciences 8:7 2012 pg 935-44

    MeSH

    Animals
    Apoptosis
    Autophagy
    Lead
    Learning
    Male
    Maze Learning
    Memory
    Phosphorylation
    Rats
    Rats, Sprague-Dawley
    alpha-Synuclein
    tau Proteins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22811615