Neuronal excitotoxicity induced by glutamatergic receptor overstimulation contributes to brain damage. Recent studies have shown that lysosomal membrane permeabilization (LMP) is involved in ischemia-associated neuronal death. In this study we evaluated the effect of neonatal hypoxia-ischemia (HI), as a model of excitotoxicity, on the lysosomal integrity throughout the distribution of the lysosomal proteins cathepsin D and prosaposin. Rat pups (7 days old) of the Wistar Kyoto strain were submitted to HI and they were euthanized 4 days after treatment and the cerebral cortex (Cx) and hippocampus (HIP) were processed for immunohistochemistry or immunoblotting. Treatment induced an increase of gliosis and also a redistribution of both prosaposin and cathepsin D (as intermediate and mature forms), into the cytosol of the HIP and Cx. In addition, HI induced a decrease of LAMP-1 in the membranous fraction and the appearance of a reactive band to anti-LAMP-1 in the cytosolic fraction, suggesting a cleavage of this protein. From these results, we propose that the abnormal release of Cat D and PSAP to the cytosol is triggered as a result of LAMP-1 cleavage in HI animals, which leads to cell damage. This could be a common mechanism in pathological conditions that compromises neuronal survival and brain function.Fil: Troncoso, Mariana Elizabeth. Universidad Nacional de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; ArgentinaFil: Bannoud, Nadia. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; ArgentinaFil: Carvelli, Flavia Lorena. Universidad Nacional de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; ArgentinaFil: Asensio, Joana Antonela. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; ArgentinaFil: Seltzer, Alicia Mabel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; ArgentinaFil: Sosa Escudero, Miguel Angel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Universidad Nacional de Cuyo; Argentin
