Seven cDNAs enriched following hippocampal lesion: possible roles in neuronal responses to injury.

Synaptic plasticity is important for formation of long-term memories and in re-establishment of function following injury. Seven cDNAs enriched following lesion in the hippocampus of the rat have been isolated using a PCR-based cDNA suppression subtraction hybridization. Sequence analysis resulted in the identification of two genes with known roles in synaptic development and neuronal activities: astrotactin and calcineurin. These two neuron-specific genes have established roles in development or synaptogenesis. Sequence analysis of the other five additional genes shows that two are likely to be involved in G-protein signaling pathways, one is a WD repeat protein, and the remaining two are entirely novel. All seven candidates are expressed in the hippocampus and, in some cases, cortical layers of adult brains. RT-PCR data show that expression increases following synaptogenic lesion. Immunocytochemical analysis in primary hippocampal neurons showed that Calcineurin immunoreactivity was redistributed in neurons during 2 weeks in culture. This redistribution suggests that Calcineurin's role changes during neurite outgrowth immediately prior to synapse formation in vitro. In addition, inhibiting Calcineurin activity with cyclosporin A enhanced neurite outgrowth, suggesting that Calcineurin has a regulatory role in axon sprouting. The discovery of previously unknown genes involved in the response to neurodegeneration will contribute to our understanding of neural development, responses to CNS trauma, and neurodegenerative diseases.