Reduced expression of NeuroD1 in the neonatal hypoxic-schemic rat brain is restored by preconditioning.

CASTRO A; LOPEZ AGUILERA, F; SAVASTANO L; SELTZER A; MUÑOZ, EM

Universidad de la Punta, Cdad. de la Punta, San Luis.

Congreso; XXVII Reunion Cientifica Anual de la Sociedad de Biologia de Cuyo. Ciudad de la Punta. Pcia de San Luis 11-13 Diciembre, 2009; 2009

Sociedad de Biologia de Cuyo

Preconditioning (PCon), is an endogenous mechanism that protects organisms against injury. It promotes the expression of genes involved in restorative mechanisms such as neurogenesis. We have induced PCon in a model of neonatal rat brain  ischemic lesion, and assessed the expression of NeuroD1, a member of the bHLH transcription factor family that is known to influence the fate of specific neuronal cells. For immunohistochemistry, PFA fixed brain slices (20 um) were obtained from  lesioned (L) (8 day-old pups  with permanent ligature of the right common carotid artery and 1-2 min of asphyxia); PCon (same as L, but submitted to 3 consecutive sessions of autohypoxia in sealed chambers on the previous day) and Control (C:sham operated- non-asphyxiated). L animals showed an enhancement of the reactive glia (GFAP+ and Vim+ astrocytes), and PCon animals, a milder reaction. NeuroD1+signal was located in the nucleus of the subgranular zone cells of the dentate gyrus (DG), of both hemispheres of C and PCon. A decrease of these labeled cells was observed in the ipsilateral damaged hippocampus. The contralateral hemisphere remained similar to C.  On the other hand, a similar NeuroD1(+) pattern to C animals was observed in the contralateral damaged hippocampus. Abundant NeuroD1(+) cells were found at the external and internal granule cell layers of the cerebellum apparently migrating from one layer to another. In tissue samples from C and PCon animals, a  cluster of NeuroD1(+) cells was observed in the cerebral cortex (CC) close to the IV ventricle, whereas in the damaged rat cerebellum it was observed lesser NeuroD1(+) labeling in migration cells, and the CC cluster disappeared. These preliminary results suggest that neonatal hypoxia-ischemic affects NeuroD1 expression  in the hippocampus and cerebellum and PCon prevents these changes.