APOPTOSIS IN SUBSTANTIA-NIGRA FOLLOWING DEVELOPMENTAL STRIATAL EXCITOTOXIC INJURY

We have previously observed that an axon-sparing injury to the develop ing striatum induced by the excitotoxin quinolinate results in a decre ase in dopaminergic neurons in the substantia nigra pars compacta (SNp c) of the adult. This decrease occurs in the absence of direct injury to the SNpc. As the striatum is a major target for the SNpc dopaminerg ic system, we have hypothesized that a decrease in the size of the str iatal target during development may result in an induced regressive ev ent in the SNpc, similar to what has been described for many developin g neural systems with peripheral targets. We have examined by morpholo gic and biochemical means the time course and character of cell death in SN following a unilateral striatal lesion with quinolinate in immat ure rats. The striatal lesion is associated with an induced cell death event in the ipsilateral SN, observed first in SNpc and then in SN pa rs reticulata. The morphologic characteristics of the dying cells were typical of apoptosis. Immunostaining for tyrosine hydroxylase indicat ed that some of the apoptotic cells in the SNpc were dopaminergic. We conclude that developmental striatal excitotoxic injury is associated with induced apoptotic cell death in SN.