Ethyl Pyruvate Rescues Nigrostriatal Dopaminergic Neurons by Regulating Glial Activation in a Mouse Model of Parkinson's Disease

    Authors

    S. H. Huh; Y. C. Chung; Y. Piao; M. Y. Jin; H. J. Son; N. S. Yoon; J. Y. Hong; Y. K. Pak; Y. S. Kim; J. K. Hong; O. Hwang;B. K. Jin

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    Abbreviated Journal Title

    J. Immunol.

    Keywords

    NITRIC-OXIDE SYNTHASE; OXIDATIVE STRESS CONTRIBUTES; RAT MESENCEPHALIC; CULTURES; MICROGLIAL NADPH OXIDASE; IN-VIVO; TYROSINE-HYDROXYLASE; HIPPOCAMPAL-NEURONS; CELL-DEATH; MPTP MODEL; NEURODEGENERATION; Immunology

    Abstract

    This study examined whether ethyl pyruvate (EP) promotes the survival of nigrostriatal dopaminergic (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. MPTP induced degeneration of nigrostriatal DA neurons and glial activation as visualized by tyrosine hydroxylase, macrophage Ag complex-1, and/or glial fibrillary acidic protein immunoreactivity. Western blotting and immunohistochemistry showed activation of microglial NADPH oxidase and astroglial myeloperoxidase (MPO) and subsequent reactive oxygen species/reactive nitrogen species production and oxidative DNA damage in the MPTP-treated substantia nigra. Treatment with EP prevented degeneration of nigrostriatal DA neurons, increased striatal dopamine levels, and improved motor function. This neuroprotection afforded by EP was associated with the suppression of astroglial MPO expression, NADPH oxidase-, and/or inducible NO synthase-derived reactive oxygen species/reactive nitrogen species production by activated microglia. Interestingly, EP was found to protect DA neurons from 1-methyl-4-phenyl-pyridinium neurotoxicity in cocultures of mesencephalic neurons and microglia but not in neuron-enriched mesencephalic cultures devoid of microglia. The present findings show that EP may inhibit glial-mediated oxidative stress, suggesting that EP may have therapeutic value in the treatment of aspects of Parkinson's disease related to glia-derived oxidative damage. The Journal of Immunology, 2011, 187: 960-969.

    Journal Title

    Journal of Immunology

    Volume

    187

    Issue/Number

    2

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    960

    Last Page

    969

    WOS Identifier

    WOS:000292451000043

    ISSN

    0022-1767

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