TEMPORAL CORRELATION BETWEEN CELLULAR DEATH AND ACTIVATION OF APOPTOTIC PATHWAYS IN A PRENATAL ACUTE HYPOXIA MODEL

S FISZER DE PLAZAS; M VACOTTO

Portland, Oregon

Congreso; 37 American Society for Neurochemistry; 2006

American Society for Neurochemistry

CNS exposure to hypoxia is associated to an increase in the release of excitatory amino acids with subsequent  activation of diverse signaling pathways  and cellular death of the apoptotic type. Our aim was to establish a temporal correlation between cellular and molecular alterations induced by normobaric acute hypoxic hypoxia (8%O2 and 92%N2, for 60 min), evaluated at different post-hypoxia (p-h) times,  at  two stages of chick optic lobe development : embryonic day (ED) 12 and 18. At ED 12, I3HI MK-801 binding assays showed  that hypoxia produced a decrease of 50% in the Bmax value of the NMDA receptor low affinity site which remained irreversible up to 6 days in normoxic conditions. TUNEL assays at ED12 disclosed a significant increase (300%) in the number of pycnotic cells in hypoxic embryos vs. controls, at 6 hs. p-h, whereas at 12 hs. no significant differences were observed. At ED18, TUNEL assays failed to show any morphological changes in hypoxic embryos vs. controls, at the same  time points. At ED 12, there was a significant increase (50%) in Bcl2 levels at the end of the hypoxic treatment, followed by a significant increase (50%) of active caspase 9  levels at 30 min. p-h and active caspase 3 levels (60%) at 60 min. p-h. At ED18, no significant changes  were observed for the three apoptotic proteins  at the same  time points. In conclusion, an acute prenatal hypoxia in developing chick optic lobe produces an equilibrated imbalance in the pro- and anti-apoptotic cell markers that finally culminates in a process of apoptotic cell death, only present at early stages of development.