Zonisamide attenuates MPTP neurotoxicity in marmosets.
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 x 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) from 159 to 319 µm² compared to the group treated with MPTP alone. This observation suggests that zonisamide reduces MPTP toxicity.
Department of Therapeutic Medicine, Ehime University Graduate School of Medicine, Japan.
Mohammed Emamussalehin
ME
Choudhury
Takashi
T
Moritoyo
Hayato
H
Yabe
Noriko
N
Nishikawa
Masahiro
M
Nagai
Madoka
M
Kubo
Seiji
S
Matsuda
Masahiro
M
Nomoto
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D002144:Callithrix; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D000078305:Zonisamide
D000978:Antiparkinson Agents; D007555:Isoxazoles; D018696:Neuroprotective Agents; D009498:Neurotoxins; D012642:Selegiline; D000078305:Zonisamide; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine