PRICE, Mitch; LANG, Molly; PATEL, Samip; FRANK, Ami; EWING, Andrew; DAY, Jonathan; The Pennsylvania State University; The Pennsylvania State University; The Pennsylvania State University; The Pennsylvania State University; The Pennsylvania State University; California State Universtiy, Chico: Functional expression of Calcineurin During Neural Response to Injury; One of Seven cDNA Enriched Following Hippocampal Lesion

Synaptic plasticity is important for formation of long-term memories and in re-establishment of function following injury. Seven cDNA 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. The association between all seven genes and the neuronal response to lesion is the direct result of a unique experimental paradigm to investigate gene expression in the brain following hippocampal lesion. Because it has been implicated previously in synaptic plasticity, Calcineurin was selected for subsequent investigation; in Rat pups calcineurin expression increases over a 3-week developmental time course and likewise, following hippocampal lesion calcineurin expression increases. Immunocytochemical analysis shows that localization of Calcineurin in primary neurons changes over a period of two weeks in culture and pharmacological inhibition of Calcineurin activity leads to increased neurite length. Overall, the discovery of previously unknown genes involved in the response to lesion should contribute to our understanding of embryonic neuronal development, responses to neuronal injury, and neurodegenerative diseases.