Differential regulation of the growth-associated proteins, GAP-43 and SCG-10, in response to unilateral cortical ablation in adult rats

Synapse replacement after brain injury has been widely documented by anatomical studies in various parts of both the developing and adult nervous system. However, the molecular events that define the specificity of the empirically derived rules of reactive synaptogenesis in different regions of the adult brain remain unclear. In this study we examined the differential regulation of the lesion-induced response of the two growth-associated proteins, superior cervical ganglia-10 and growth-associated protein-43, after unilateral cortex ablation, and determined a hierarchical order for the lesion response from remaining afferent projection neurons originating from the contralateral cortex, ipsilateral thalamus and substantia nigra. We report that in response to unilateral cortex ablation both messenger RNA, by northern blot, and protein, by estern blot, for superior cervical ganglia-10 but not growth-associated protein-43 was increased in the homologous area of the contralateral cortex but not the ipsilateral thalamus or substantia nigra. In addition, the specificity of the superior cervical ganglia-10 response, assessed by combined in situ hybridization and retrograde FluoroGold labeling of striatal afferent neurons, found that superior cervical ganglia-10 messenger RNA was increased prominently in layer V pyramidal neurons of the contralateral corticostriatal pathway but was unchanged in afferent projection neurons from the thalamus and substantia nigra. Furthermore, the increase in both superior cervical ganglia-10 messenger RNA and protein seen at three days postlesion in contralateral corticostriatal neurons coincides in time with the initiation of neurite outgrowth in the deafferented striatum by contralateral corticostriatal axons described in our previous ultrastructural study. However, if cortical input to the striatum was removed bilaterally the lesion-induced response for superior cervical ganglia-10 messenger RNA shifted secondarily to thalamostriatal neurons in the ipsilateral thalamus.

These data provide evidence that superior cervical ganglia-10 and growth-associated protein-43 are differentially regulated in neurons of the contralateral corticostriatal pathway in response to unilateral cortex ablation and suggests that superior cervical ganglia-10 plays a role in the regulation of neurite outgrowth in the adult striatum after brain injury. However, the specific role that superior cervical ganglia-10 may play in reactive synaptogenesis remains unclear. In addition, our data suggest that a hierarchical order exists for the reinnervation of deafferented striatal neurons after unilateral cortex ablation with preference given to homologous axons from the contralateral cortex.