Therapeutic effect of a novel anti-parkinsonian agent zonisamide against MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) neurotoxicity in mice.
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.
Yokoyama
Hironori
H
Department of Neurobiology and Therapeutics, Institute of Health Bioscience, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima, Japan.
Yano
Ryohei
R
Kuroiwa
Hayato
H
Tsukada
Tatsuya
T
Uchida
Hiroto
H
Kato
Hiroyuki
H
Kasahara
Jiro
J
Araki
Tsutomu
T
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D000078305:Zonisamide
D000975:Antioxidants; D000978:Antiparkinson Agents; D007555:Isoxazoles; D018696:Neuroprotective Agents; D000078305:Zonisamide; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine