IGF-1 Alleviates NMDA-Induced Excitotoxicity in Cultured Hippocampal Neurons Against Autophagy via the NR2B/PI3K-AKT-mTOR Pathway

摘要: Insulin-like growth factor-1 (IGF-1) is a brain-specific multifunctional protein involved in neuronal polarity and axonal guidance. Mature IGF-1 triggers three enzymes, mitogen-activated kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), phosphoinositide phospholipase C-γ (PLC-γ), which are its predominant downstream regulators. The PI3K-AKT signaling pathway upstream of the mammalian target rapamycin (mTOR), great importance induction autophagy. However, whether neuroprotective effect against excitotoxicity mediated by autophagy through PI3K/AKT/mTOR remains to be elucidated. following NMDA treatment was determined microtubule-associated light chain 3 (LC3) conversion result this assessed monitoring cleavage caspase cultured hippocampal neurons. Cell viability using MTT LDH assay, PI-staining used estimate fate protective IGF-1. In addition, found decrease induced transmission electron microscopy MDC staining. accompanied with up-regulation phospho-AKT (p-AKT) phospho-mTOR (p-mTOR), blocked inhibitor PI3K. At same time, activation NR2B resulting down-regulation p-AKT p-mTOR Together, these data suggest that induces autophagy, followed apoptosis neurons, can block via inhibition receptors PI3K-AKT-mTOR pathway.