Neurotrophins and Neuroprotection in a prenatal hypoxic model

S. FISZER DE PLAZAS, MARÍA EUGENIA BOGETTI.

Washington

Congreso; Society for Neuroscience; 2011

Naturally ocurring cell death (NOCD) is a process that occurs in the developing CNS, as a result of an excess of neuroblast generated early in development and for refinement and specificity of the neuronal connections. It´s necessary to guarantee the final citoarchitecture and correct wiring of the nervous system. In contrast, hypoxia is an injury that consists of decreased O2 concentration in blood and tissues, leading to cell dead. This cell death could be necrotic, apoptotic or somewhere between both, depending on the intensity of the injury, duration, region, cell type involved, developing stage, etc. On the other hand, apoptosis is the only mechanism that executes NOCD. In our developmental model, both NOCD and hypoxic cell death (HxCD) coexist, making it interesting to analyse similarities or differences between the triggers, the early events and the execution pathways involved in both process. Mainly there are two pathways for execution of apoptosis, the intrinsic and the extrinsic, requiring or not mitochondria respectively. The intrinsic pathway consists on the formation of a mitochondrial pore in the external membrane that releases cytochrome C (Cyt C) among other factors. The Cyt C forms a complex with apaf-1, caspase-9 and ATP named apoptosome. The activation of caspase-9 in turn, cleaves caspase-3 which acts over many targets proteins that leads to the classic apoptotic phenotype. As hypoxia directly affects mitochondrial homeostasis, the key steps of the intrinsic pathway will be compared for NOCD and HxCD.