PRECONDITIONING-INDUCED NEUROGENESIS IS MEDIATED BY NeuroD1 IN THE NEONATAL RAT MODEL OF HYPOXIA-ISCHEMIA.

A.CASTRO; V. ORTIZ MALDONADO; L. SAVASTANO; S. BENITEZ; M. FITT; A. SELTZER; E. MUÑOZ

Uspallata, Mendoza, Argentina

Congreso; V Neurotoxicity Society Meeting; 2011

NeuroD1 is a bHLH transcription factor involved in neuronal differentiation and migration. During brain development, post-natal period and adulthood, NeuroD1 expression is restricted to the cerebellum, hippocampus and pineal gland. Preconditioning (PC), on the other hand, is a mechanism that protects tissues against injury and it is thought to induce neurogenesis. In this work, we studied the effects of PC on NeuroD1 expression in neonatal hypoxic-ischemic rat via immunohistochemistry and western blot. The following groups were studied: control (C: sham-operated non-asphyxiated pups); lesioned (L: P8 pups with permanent ligature of the right CCA, followed by 1-2 min asphyxia) and preconditioned (PC: pups in auto-hypoxic environment before brain injury). NeuroD1 analysis was carried out using P15 pups; fixed brain slices and homogenates were used. In C, NeuroD1-positive cells were observed in the sub- and granular layers of the hippocampal dentate gyrus and in the cerebellar external and internal granule cell layers. Immunoreactive migrating cells were present in the hippocampal hilus and between both cerebellar layers. In L, we observed a decrease in NeuroD1-positive migrating cells in both brain areas. In PC, a global enhancement of NeuroD1 expression and an increase in NeuroD1-migrating cells were evident in hippocampus and cerebellum. WB analysis of NeuroD1 protein confirmed these results. In conclusion, preconditioning might protect neonatal rat brain against injury via induction of the proneural gene NeuroD1.