NGF AND NEUROPROTECTION UNDER ACUTE HYPOXIA: ROLE OF THE MEMBRANE RECEPTOR P-TrkA

S. FISZER DE PLAZAS, M. EUGENIA BOGETTI

San Diego

Congreso; Society for Neuroscience; 2013

Society for Neuroscience

The decrease in the concentration of oxygen in the blood and tissues (hypoxia) constitutes an insult of important consequences given the irreversibility of the damages caused in the Central Nervous System, both during development and in the adult life. Our model of acute hypoxia on embryonated chicken eggs (Gallus gallus, 60 min, 8% O2) and in primary neuronal cultures (4 hours, 0.5% O2) showed negative effects on neurons in the optic tectum (OT) on day 15 of development. Embryonic day (ED) 15 was established to carry out the studies because it is a period in which Neurotrophins (NTFs) play an essential role in the maintenance and survival of neurons. The aims of the present work were to determine the expression of the Nerve Growth Factor (NGF) and its receptors in membrane P-TrkA and p75 in response to hypoxic damage and to assess the possible neuroprotective role of NGF and the pathways involved in this injury. In vivo, the lower amount of neurons (close to 60%) observed as a result of acute hypoxia was accompanied by a variation in the expression of NGF and its membrane receptors in membrane, P-TrkA and p75. The increase in the labeling of NGF is interpreted as a strategy of neurons to counteract the damage produced, given the participation of NGF in activating survival pathways. The phosphorylation of TrkA was diminished at the end of hypoxia (H0), whereas p75 expression (related to cell death pathways) showed no changes, which could partly explain the neuronal death evidenced 6 hours after the damage. A lower phosphorylation of TrkA was also observed in primary cultures of neurons in the OT of ED15 embryos. The addition of NGF (50 ng/ml) to the culture medium prior to the hypoxic injury prevented the increase in the neuronal apoptotic death rate and the decrease in phosphorylation of the receptor, which could be one of the events that may explain the neuroprotective effect of this neurotrophin. The addition of the inhibitor of P-TrkA k252a inhibited the neuroprotective effect of NGF. This would support the hypothesis that the neuroprotection phenomenon occurs through a pathway in which P-TrkA would be a key initial molecule.