CONICET | Buscador de Institutos y Recursos Humanos

A decrease in the concentrationof oxygen in the blood and tissues (hypoxia) produces important, sometimesirreversible, damages in the central nervous system (CNS) both duringdevelopment and also postnatally. The present work aims at analyzing theexpression of nerve growth factor (NGF) and p75 and the activation of TrkA inresponse to an acute normobaric hypoxic event and to evaluate the possibleprotective role of exogenous NGF. Thedeveloping chick optic tectum (OT), a recognized model of corticogenesis, wasused as experimental system by means of in vivo and in vitro studies.Based on identification of theperiod of highest sensitivity of developmental programmed cell death (ED15) we show that hypoxia has a mild but reproducibleeffect that consist of a temporal increase of cell death 6 h after the end of ahypoxic treatment. Cell death was preceded by a significant early increase inthe expression of Nerve Growth Factor (NGF) and its membrane receptor p75. In addition, we found a biphasic response of TrkAactivation: a decrease during hypoxia followed by an increase -4 hours later- thattemporally coincide with the interval of NGF overexpression. To test the NGF - NGFreceptors role in hypoxic cell death, we quantified, in primary neuronalcultures derived from ED15 OT, the levels of TrkA activation after an acutehypoxic treatment. A significant decline in the level of TrkA activation wasobserved during hypoxia followed, 24 h later, by significant cell death. Interestingly,this cell death can be reverted if TrkA inactivation during hypoxia issuppressed by the addition of NGF. Our results suggest that TrkAactivation may play an important role in the survival of OT neurons subjectedto acute hypoxia. The role of TrkA in neuronal survival after injury may beadvantageously used for the generation of neuroprotective strategies to improveprenatal insult outcomes.