Effect of striatal lesion with quinolinate on the development of substantia nigra dopaminergic neurons: a quantitative morphological analysis.

We have previously reported that a developmental axon-sparing striatal injury induced by hypoxia-ischemia results in a diminished adult number of substantia nigra (SN) tyrosine hydroxylase (TH)-positive neurons, in the absence of direct nigral injury. To examine the specific role of striatal injury, we made selective striatal lesions in the 7-day-old rat with quinolinic acid (QA), 40, 80, 120 and 480 nmol. Striatal lesions resulted in a decrease in the adult number of TH-positive neurons in the ipsilateral SN. The decrease was correlated with the reduction in striatal area (r = 0.76, p < 0.01); a 25-30% reduction in SN neurons was observed at 50-60% striatal area loss. The area of SN pars compacta (SNpc) in animals with 120- and 480-nmol QA lesions was reduced by 12 and 15%, respectively (p < 0.01) and this reduction also correlated with the loss of striatal area (r = 0.63, p < 0.01). Individual TH-positive neuron size and neuron-packing density were unaltered in SNpc on the experimental side. We conclude that the adult number of SN dopaminergic neurons depends on developmental support by the striatum. We hypothesize that less support by the smaller striatum may result in accentuated developmental cell death in the SNpc.