Zonisamide Attenuates MPTP Neurotoxicity in Marmosets

• Main Authors: Mohammed Emamussalehin Choudhury (Author), Takashi Moritoyo (Author), Hayato Yabe (Author), Noriko Nishikawa (Author), Masahiro Nagai (Author), Madoka Kubo (Author), Seiji Matsuda (Author), Masahiro Nomoto (Author)
• Format: Book
• Published: Elsevier, 2010-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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 zonis amide, 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. Keywords:: MPTP, tyrosine hydroxylase (TH)-positive dopaminergic neuron, selegiline, zonisamide, marmoset

Item Description

1347-8613
10.1254/jphs.10120FP