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Therapeutic effect of a novel anti-parkinsonian agent zonisamide against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)neurotoxicity in mice

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Abstract

We investigated the therapeutic effect of zonisamide against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice, using Western blot analysis, immunohistochemistry and behavioral test. Our Western blot analysis and immunohistochemical study showed that the post-treatment with zonisamide prevented significantly dopaminergic cell damage, the depletion of tyrosine-hydroxylase (TH) protein levels and the proliferation of microglia in the striatum and/or substantia nigra 8 days after MPTP treatment. Furthermore, our behavioral study showed that the post-treatment with zonisamide attenuated significantly the motor deficits 7 days after MPTP treatment. These results show that zonisamide has the therapeutic effect in the MPTP model of Parkinson’s disease (PD) in mice. Our study also demonstrates the neuroprotective effect of zonisamide against dopaminergic cell damage after MPTP treatment in mice. Thus our present findings suggest that therapeutic strategies targeted to the activation of TH protein and/or the inhibition of microglial activation with zonisamide may offer a great potential for restoring the functional capacity of the surviving dopaminergic neurons in individuals affected with PD.

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Acknowledgements

This study was supported in part by Grant-in-Aid for Scientific Research (136700627 and 13671095) from the Ministry of Science and Education in Japan.

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Authors and Affiliations

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

    Hironori Yokoyama, Ryohei Yano, Hayato Kuroiwa, Tatsuya Tsukada, Hiroto Uchida, Jiro Kasahara & Tsutomu Araki

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

    Hiroyuki Kato

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  1. Hironori Yokoyama
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  2. Ryohei Yano
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  3. Hayato Kuroiwa
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  5. Hiroto Uchida
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  6. Hiroyuki Kato
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  8. Tsutomu Araki
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Correspondence to Tsutomu Araki.

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Yokoyama, H., Yano, R., Kuroiwa, H. et al. Therapeutic effect of a novel anti-parkinsonian agent zonisamide against MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)neurotoxicity in mice. Metab Brain Dis 25, 135–143 (2010). https://doi.org/10.1007/s11011-010-9191-0

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