Zonisamide Attenuates MPTP Neurotoxicity in Marmosets
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- Choudhury Mohammed Emamussalehin
- Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan
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- Moritoyo Takashi
- Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan
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- Yabe Hayato
- Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan
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- Nishikawa Noriko
- Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan
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- Nagai Masahiro
- Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan
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- Kubo Madoka
- Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan
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- Matsuda Seiji
- Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Japan
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- Nomoto Masahiro
- Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan
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Abstract
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) induces parkinsonism in humans and animals. The effects of zonisamide on dopamine neurons were studied in MPTP-treated common marmosets (Callithrix jacchus). Groups of animals (n = 3) were treated with MPTP (2.5 mg/kg, every 24 h × 3); MPTP plus zonisamide (40 mg/kg administered 1 h before each MPTP dose); MPTP plus selegiline (a known MAO-B inhibitor) (2 mg/kg administered 1 h before each MPTP dose); and saline controls. An immunohistochemical study of the substantia nigra was performed 14 days after MPTP treatment in each group. MPTP reduced the mean number of tyrosine hydroxylase (TH)-positive neurons to 10% of the normal control group and mean cell size was significantly (P < 0.001) reduced from 424 to 159 μm2. In the group pre-treated with zonisamide, the mean number of TH-positive neurons was reduced to 26% of that in the normal control group and the mean neuron size was significantly (P < 0.05) increased from 159 to 273 μm2 compared with the group treated with MPTP alone. Moreover, in the group pre-treated with selegiline, the mean number of TH-positive neurons was 47% of that in the normal control group and the mean neuron size was increased significantly (P < 0.01) from159 to 319 μm2 compared to the group treated with MPTP alone. This observation suggests that zonisamide reduces MPTP toxicity.
Journal
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 114 (3), 298-303, 2010
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390001205180648320
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- NII Article ID
- 10029890426
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- NII Book ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL BIB ID
- 10887901
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed