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Delayed Treatment with Arundic Acid Reduces the MPTP-induced Neurotoxicity in Mice

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Abstract

The authors investigated the protective effects of a novel astrocyte-modulating agent, arundic acid, in a 1-methyl-4-phenyl-1,2,3,6-tetrahyropyridine (MPTP) mouse model of Parkinson’s disease. Male mice received four intraperitoneal (i.p.) injections of MPTP (20 mg/kg) at 2 h intervals. The content of dopamine and its metabolites in the striatum was reduced markedly 7 days after MPTP treatment. The delayed treatment with arundic acid (30 mg/kg, i.p.) administered 3, 4, 5 and 6 days after MPTP treatment did not affect the depletion of dopamine and its metabolites in the striatum. Our immunohistochemical study with anti-tyrosine hydroxylase antibody, anti-neuronal nuclei antibody, anti-glial fibrillary acidic protein antibody, anti-S100β antibody and anti-nestin antibody showed that the delayed treatment with arundic acid had a protective effect against MPTP-induced neuronal damage in the striatum and the substantia nigra of mice. Furthermore, this agent ameliorated the severe reductions in number of isolectin reactive microglia in the striatum and the substantia nigra 7 days after MPTP treatment. These results demonstrate that the inhibition of S100β synthesis in astrocytes may be the major component of the beneficial effect of arundic acid. Thus, our present findings provide that the therapeutic strategies targeted to astrocytic modulation with arundic acid offers a great potential for restoring the functional capacity of the surviving dopaminergic neurons in individuals affected with Parkinson’s disease.

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Acknowledgements

This study was supported in part by the Grant-in-Aid for Scientific Research (12877163, 13671095 and 13670627) from the Ministry of Science and Education in Japan.

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Authors and Affiliations

  1. Department of Neurobiology and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78, Sho-machi, Tokushima, 770-8505, Japan

    Chie Oki, Yu Watanabe, Hironori Yokoyama & Tsutomu Araki

  2. Project Management, Research Headquarters, Ono Pharmaceutical Co. Ltd, Osaka, Japan

    Taiji Shimoda

  3. Department of Neurology, Organized Center of Clinical Medicine, International University of Health and Welfare, Tochigi, Japan

    Hiroyuki Kato

Authors
  1. Chie Oki
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  2. Yu Watanabe
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  3. Hironori Yokoyama
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  4. Taiji Shimoda
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  5. Hiroyuki Kato
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  6. Tsutomu Araki
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Correspondence to Tsutomu Araki.

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Oki, C., Watanabe, Y., Yokoyama, H. et al. Delayed Treatment with Arundic Acid Reduces the MPTP-induced Neurotoxicity in Mice. Cell Mol Neurobiol 28, 417–430 (2008). https://doi.org/10.1007/s10571-007-9241-2

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  • DOI: https://doi.org/10.1007/s10571-007-9241-2

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