Hypoxia Induced cell death is modulated by neurotrophins in developing CNS

FISZER DE PLAZAS, S; BOGETTI, ME; POZO DEVOTO, V M

San Diego, CAlifornia

Congreso; Neuroscience 2010, Annual Meeting of the Society for Neuroscience; 2010

SFN

The decrease in the availability of oxygen during embryonic development causes irreversible damage to the CNS. Previous results in our model of acute hypoxia (60 min, 8% of O2) in chicken embryos have shown that discrete and delayed neuronal death, presenting the apoptotic phenotype and occurring through the intrinsic mitochondrial pathway, is produced in the optic tectum (OT) on embryonic day (ED) 12. In order to evaluate the possible influence of retinal ganglion cells on the OT, embryos were enucleated on ED 3 and then left to develop until ED12. The results showed no significant changes in the number of TUNEL+ cells per OT on ED12 between contralateral (without fibers, Contra) and ipsilateral (with fibers, Ipsi) OT, either in the naturally occurring neuronal death (Ipsi vs. Contra, 308 ±37 vs. 319 ±38) or that generated by hypoxia (Ipsi vs. Contra, 683 ±103 vs. 670 ±74). On the other hand, the Western Blot showed that hypoxia decreased the levels of pAkt (Control vs. Hypoxia, 100 vs, 49), which returned to normal values between 30 and 90 minutes post-hypoxia (85 ±4 and 89 ±4). Because of the close relationship between the PI3K/Akt pathway and neurotrophins, in our experimental model we determined the second wave of naturally occurring cell death (known as neurotrophic), which occurred between ED 14 and ED 16 (number of TUNEL+ neurons/mm2 on ED 13: 368±31.5, ED 14: 378±32.3, ED 15: 416±21, ED 16: 308±22.04, ED 17: 96± 8.7, ED18: 12±8.7, p