Age-associated changes in synaptic PI3K/AKT/GSK3 beta signaling during iron-induced neurotoxicity

URANGA, ROMINA MARÍA; GIUSTO, NORMA MARÍA; SALVADOR, GABRIELA ALEJANDRA

San Miguel de Tucumán, Tucumán, Argentina

Congreso; XLV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Phosphoinositide 3-kinase (PI3K)/Akt pathway and its downstream effector glycogen synthase kinase 3 beta (GSK3 beta) are key signaling pathways involved in synaptic plasticity and neuronal survival. In this work, the participation of synaptic PI3K/Akt/GSK3 beta signaling during iron-induced oxidative injury was characterized. Cerebral cortex synaptosomes obtained from adult and aged rats were exposed to Fe2+ (50 microM) for different periods of time and synaptosomal viability and the state of the PI3K/Akt/GSK3 beta pathway were evaluated. Mitochondrial function (MTT reduction), plasma membrane integrity (LDH leakage) and reactive oxygen species (DCF probe) were significantly affected in both age groups. However, aged animals showed a greater susceptibility to oxidative injury. In adults, Akt and GSK3 beta were activated only after 5 min, whereas in aged animals activation occurred after 5 and 30 min of incubation with the metal ion. Both Akt and GSK3 beta phosphorylation were dependent on PI3K activation. ERK1/2 activation was PI3K-dependent in adults, whereas in aged animals ERK1/2 activation was a PI3K-independent event and showed higher levels than that observed in adults. Results demonstrate that synaptic endings from aged animals undergo a greater susceptibility to iron-induced neurotoxicity with a differential profile in the activation of PI3K/Akt/GSK3 beta.