Axotomy-induced differential gene induction in neurons of the locus ceruleus and substantia nigra.

The biochemical and molecular events correlated with neuronal injury and survival are not well understood. Previous studies have reported that following axotomy, neurons in the substantia nigra pars compacta (SNc) and the locus ceruleus (LC) exhibit a significant increase in tyrosine hydroxylase (TH) enzyme activity within 24-72 h (Brain Res., 144 (1978) 325-342; Brain Res., 92 (1975) 57-72). To investigate the potential contribution of TH gene induction to this increase a semi-quantitative immunocytochemical and in situ hybridization time course analysis was undertaken. Following axotomy, TH immunoreactivity increased in neurons of both the SNc and LC. In contrast, an increase in TH mRNA was only evident in neurons of the LC. As a possible mechanism for the observed alterations in TH gene expression, the levels of an immediate early gene, c-fos, were examined. C-fos mRNA and Fos protein were not expressed in either normal or axotomized neurons of the SNc. However, the constitutive expression in control LC neurons increased significantly following axotomy. These data demonstrate the differential response of two central catecholaminergic populations to axotomy and suggests a potential role for the immediate early gene, c-fos, in the post-injury reaction.