The degeneration of dopaminergic synapses in Parkinson's disease: A selective animal model.

Abstract

Available evidence increasingly suggests that the degeneration of dopamine neurons in Parkinson’s disease starts in the striatal axons and synaptic terminals. A selective procedure is described here to study the mechanisms involved in the striatal denervation of dopaminergic terminals. This procedure can also be used to analyze mechanisms involved in the dopaminergic re-innervation of the striatum, and the role of astrocytes and microglia in both processes. Adult Sprague-Dawley rats were injected in the lateral ventricles with increasing doses of 6-hydroxydopamine (12–50 g), which generated a dose-dependent loss of dopaminergic synapses and axons in the striatum, followed by an axonal sprouting (weeks later) and by a progressive recovery of striatal dopaminergic synapses (months later). Both the degeneration and regeneration of the dopaminergic terminals were accompanied by astrogliosis. Because the experimental manipulations did not induce unspecific damage in the striatal tissue, this method could be particularly suitable to study the basic mechanisms involved in the distal degeneration and regeneration of dopaminergic nigrostriatal neurons, and the possible role of astrocytes and microglia in the dynamics of both processes.