Zonisamide Attenuates MPTP Neurotoxicity in Marmosets

• Choudhury Mohammed Emamussalehin

  Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan

• Moritoyo Takashi

  Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan

• Yabe Hayato

  Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan

• Nishikawa Noriko

  Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan

• Nagai Masahiro

  Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan

• Kubo Madoka

  Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan

• Matsuda Seiji

  Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Japan

• Nomoto Masahiro

  Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan

抄録

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.

収録刊行物

• Journal of Pharmacological Sciences

  Journal of Pharmacological Sciences 114 (3), 298-303, 2010

  公益社団法人 日本薬理学会

キーワード

• MPTP
• tyrosine hydroxylase (TH)-positive dopaminergic neuron
• selegiline
• zonisamide
• marmoset

詳細情報

• CRID: 1390001205180648320
• NII論文ID: 10029890426
• NII書誌ID: AA11806667
• DOI: 10.1254/jphs.10120fp
• ISSN: 13478648
• ISSN: 13478613
• NDL書誌ID: 10887901
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10887901
• Web Site: https://search.jamas.or.jp/link/ui/2011206301
• 本文言語コード: en
• データソース種別:
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