Biochemical and immunocytochemical changes induced by intrastriatal 6-hydroxydopamine injection in the rat nigrostriatal dopamine neuron system: evidence for cell death in the substantia nigra.

Biochemical and immunocytochemical changes after unilateral 6-hydroxydopamine (6-OHDA) injection into the striatum were investigated in the rat nigrostriatal dopamine (DA) neuron system. Four weeks after 6-OHDA injection into the striatum, concentrations of DA and its metabolites were specifically decreased in the substantia nigra (SN), as well as in the striatum, ipsilateral to the injection. Immunocytochemistry of tyrosine hydroxylase (TH) revealed a marked decrease in the number of TH-immunoreactive neuronal cell bodies in the SN ipsilateral to the injection; this effect appeared 2 weeks after the injection and remained even 10 months after the injection. Electron microscopic study of these periods demonstrated degenerative neurons in the SN pars compacta, suggesting that the degenerative changes persisted for a long time after a single injection of 6-OHDA into the striatum. The results showed that degeneration of the dopaminergic terminals in the striatum may lead to cell death of the parent cell bodies in the SN and suggest that the striatum may be the initial site in which the neurodegeneration occurs in Parkinson's disease.