Glial responses associated with dopaminergic striatal reinnervation following lesions of the rat substantia nigra

Abstract

Lesioning of dopaminergic substantia nigra pars compacta (SNpc) neurons leads to depletion of dopamine (DA) and dopaminergic axons in the dorsal striatum, followed by subsequent compensatory sprouting of dopaminergic fibers and striatal reinnervation. In this study, the response of striatal glia (microglia and astroglia) was compared with the degeneration and regeneration of dopaminergic axons following SNpc lesions. Following partial SNpc lesions, density of dopamine transporter (DAT) immunoreactive (-ir) terminals in the dorsal striatum returned to normal within 16 weeks of injury, suggesting that dopaminergic reinnervation of the striatum was complete. In conjunction, the glial responses in the dorsal striatum consisted of two peaks. The first peak in glial density occurred immediately after lesioning, peaking at 7 days, implying that it was likely to be associated with removal of debris from degenerating terminals. The second glial response commenced 8 weeks after lesioning and peaked some time after 16 weeks. The time of onset of the second peak suggests that it may be associated with the establishment of synapses rather than with axonal guidance.