Lessons from nature: Signaling cascades associated with vertebrate brain anoxic survival

Mammalian neurons undergo rapid degeneration when oxygen supply is curtailed. Neuroprotective pathways are induced during hypoxia/ischemia but their analysis is complicated by concurrent pathological events. Survival mechanisms can be investigated in anoxia tolerant freshwater turtle species, which survive oxygen deprivation and post-anoxic reoxygenation by entrance into a state of reversible hypometabolism. Many energy demanding processes are suppressed, including ion flux and neurotransmitter release, while cellular and protective mechanisms including certain MAP Kinases are upregulated. This superfamily of serine/threonine kinases plays a significant role in vital cellular processes including cell proliferation, differentiation, stress adaptation, and apoptosis in response to external stimuli. Here we report that neuronal survival relies on robust coordination between the major signaling cascades: upregulation of the pro-survival Akt and ERK1/2 and suppression of the p38MAPK and JNK pathways. Other protective responses, including the upregulation of heat shock proteins (HSPs) and antioxidants, allow the turtle brain to abrogate potential oxidative stress upon reoxygenation.

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