Leptin-mediated cell survival signaling in hippocampal neurons mediated by JAK STAT3 and mitochondrial stabilization.

摘要: Leptin plays a pivotal role in the regulation of energy homeostasis and metabolism, primarily by acting on neurons hypothalamus that control food intake. However, leptin receptors are more widely expressed brain suggesting additional, as yet unknown, functions leptin. Here we show both embryonic adult hippocampal express coupled to activation STAT3 phosphatidylinositol 3-kinase-Akt signaling pathways. protects against cell death induced neurotrophic factor withdrawal excitotoxic oxidative insults. The neuroprotective effect is antagonized JAK2-STAT3 inhibitor AG-490, decoy DNA, 3-kinase/Akt inhibitors but not an MAPK. induces production manganese superoxide dismutase anti-apoptotic protein Bcl-xL, stabilizes mitochondrial membrane potential lessens stress. receptor-deficient mice (db/db mice) vulnerable seizure-induced damage, intraventricular administration seizures. By enhancing resistance apoptosis excitotoxicity, our findings suggest serves function developing hippocampus.