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Astrocytic Responses to the Dopaminergic Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in Cat and Mouse Brain

Abstract Glial fibrillary acidic protein immunohistochemistry was used as a selective marker for regional reactive gliosis in the striatum and ventral mesencephalon in cats and mice exposed to the dopaminergic neurotoxin 1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine. Thirty mice (C-57 black strain) were injected with 30 mg/kg intraperitoneally (IP) MPTP-HCI for seven days. Five adult cats were injected with 10 mg/kg IP MPTP-HCI for seven days. Animals were killed five to seven days after the last MPTP injection. Reactive gliosis was observed throughout the mouse striatum but not in the substantia nigra. In contrast, reactive gliosis was topographically represented in the cat caudate nucleus with a dorsal-ventral and medial-lateral gradient evident. Gliosis was also observed in the putamen and the substantia nigra, pars compacta. Tyrosine hydroxylase immunocytochemistry revealed a loss of dopamine in the mouse striatum but no loss of substantia nigra neurons. Nigral neurons were destroyed in the cat. These results suggest that MPTP may destroy nigrostriatal dopamine cell bodies and terminals in the cat while destruction in the mouse is at least initially confined to striatal terminals.