Objective Based on growing evidence linking autophagy to ischemic preconditioning,it was hypothesized that autophagy was necessary for neuroprotection conferred by hypoxic preconditioning and further aimed to test whether brain-derived neurotrophic factor(BDNF) protects against hypoxic neuronal damage by autophagy activation and the possible signaling pathway. Methods Primary cultured cortical neurons of pregnant rats were treated with oxygen deprivation (OD) for 0.5~6 h to mimic hypoxic injury in vivo.Neuronal autophagy was measured with expression of microtubule associated protein light chain 3(LC3),and the LC3II,p-Akt,p-mTOR,and p-p70S6K protein were detected by western-blot after treated with autophagy promotor rapamycin or autophagy inhibitor 3-methyladenine(3-MA). Results 1)Compared with the control group,cells treated with 50 μg/L BDNF had the highest cell viability.2)BDNF decreased the expression of P-Akt,p-mTOR,and p-p70S6K,and increased the expression of LC3II.Similar to the roles of rapamycin to the signals,BDNF-induced up-regulation of LC3II was inhibited by 3-MA. Conclusion BDNF protects cortical neurons against oxygen deprivation damage by autophagy via PI3K/Akt/mTOR/p70S6K signaling pathway.
Key words
brain-derived neurotrophic factor /
autophagy /
cortical neurons /
mammalian target of rapamycin /
light chain 3
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