Axonal sprouting following lesions of the rat substantia nigra

Parkinson's disease is characterized by the progressive loss of dopaminergi c neurons in the substantia nigra pars compacta. Symptoms do not appear unt il most nigral neurons are lost, implying that compensatory mechanisms are present. Sprouting has been proposed as one of these mechanisms. This study quantified the extent of compensatory axonal sprouting following injury of dopaminergic neurons within the substantia nigra pars compacta. Specifical ly, the extent of the axonal arbour and axonal varicosity morphology was me asured after partial destruction (with 6-hydroxydopamine) of the substantia nigra of the adult male rat. Four months later, the substantia nigra was i njected with the anterograde neuronal tracer dextran-biotin to trace the fu ll extent of individual axons. An unbiased estimate of neuron number was pe rformed in each animal. This demonstrated nigral neuronal loss ranging from 10 to 90% on the side that received the injection whilst a 7% reduction wa s observed in the side contralateral to the lesion. Coincident with this lo ss, some nigral neurons lose tyrosine hydroxylase expression. Vigorous axon al sprouting was observed in the terminal arbours of lesioned animals and w as associated with an increased axonal varicosity size. Axonal varicosities and branching points were primarily confined to the dorsal 1.5 mm of the c audate-putamen, an area predominantly innervated by nigral neurons. It appe ars that dopaminergic neurons were responsible for this sprouting because t he density of dopamine transporter immunoreactive varicosities in the cauda te-putamen was maintained until about a 70% loss of neurons. It was conclud ed that substantial compensation in the form of sprouting and new dopaminer gic synapse formation occurs following lesions of the substantia nigra pars compacta. (C) 2000 IBRO. Published by Elsevier Science Ltd.