Long-term changes in morphology, D2R expression and targets of regenerated dopaminergic terminals in the striatum after a partial lesion in the substantia nigra in the rat.

ABSTRACT

During Parkinson's disease (PD), compensatory regeneration or sprouting of fibers from surviving dopaminergic neurons in the striatum occurs in response to the lesion in the substantia nigra pars compacta (SNpc). The morphological characteristics of regenerated terminal have previously been shown to differ from normal terminals. Here, we provide insights into the morphological characteristics of regenerated dopaminergic terminals in the striatum over a 16-week period after a partial SNpc lesion. The dopaminergic fibers were almost completely lost in the dorsal part of the striatum 2weeks after the lesion, but returned to normal by 16weeks with an equal degree of dopaminergic neuron lesions in the SN at both time points. Morphologically, the regenerated dopaminergic terminals in the striatum were larger in size and had more small and large vesicles with a down-regulation of D(2) dopamine receptor (D(2)R). These terminals were more frequently in contact with D(2)R bearing neurons than D(1)R bearing neurons in the striatum. Therefore, the results indicate that dopaminergic fibers did regenerate in the dorsal part of the striatum after the SNpc lesion. Their morphological characteristics intuitively indicate that they were capable of delivering larger amounts of dopamine (DA) to compensate for the depletion, and to balance the secretion and re-uptake of DA after the lesion. The targeted change in regenerated dopaminergic terminals may disrupt the balance between the direct and indirect pathways in the basal ganglia, thereby resulting in the onset of PD symptoms.