Zonisamide Attenuates MPTP Neurotoxicity in Marmosets

Journal of Pharmacological Sciences

Madoka Kubo¹  Noriko Nishikawa¹  Hayato Yabe¹  Masahiro Nomoto¹  Seiji Matsuda²  Masahiro Nagai¹  Mohammed Emamussalehin Choudhury¹  Takashi Moritoyo¹ 

[1] Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan;Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Japan

关键词: MPTP;    tyrosine hydroxylase (TH)-positive dopaminergic neuron;    selegiline;    zonisamide;    marmoset;   

DOI  :  10.1254/jphs.10120FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(24)Cited-By(4)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.

【 授权许可】

Unknown