Increased phosphorylation of mTOR is involved in remote ischemic preconditioning of hippocampus in mice

Abstract

Different signaling pathways are involved in tissue protection against ischemia reperfusion (IR) injury, among them mammalian target of rapamycin (mTOR) and related pathways have been examined in many recent studies. Present study evaluated the role of mTOR in remote ischemic preconditioning (RIPC) of hippocampus. Renal ischemia was induced (3 cycles of 5min occlusion and 5min reperfusion of unilateral renal artery) 24h before global brain ischemia (20min bilateral common carotid artery occlusion). Saline or rapamycin (mTOR inhibitor; 5mg/kg, i.p.) was injected 30min before RIPC. mTOR and phosphorylated mTOR (p-mTOR) expression, superoxide dismutase (SOD) activity and retention trial of passive avoidance test were determined 24h after global ischemia. Apoptosis and neuronal cell density were assessed 72h after hippocampal ischemia. RIPC decreased apoptosis (p<0.05 vs. IR), improved memory (p<0.05 vs. IR), and augmented p-mTOR expression and SOD activity after hippocampal ischemia (p<0.05 vs. IR). Rapamycin abolished all protective effects of RIPC (p<0.05 vs. RIPC+IR) suggesting a role for mTOR in RIPC induced hippocampal protection.

Keywords: ATP sensitive potassium channels; Apoptosis; CCA; Common carotid artery; IR; Ischemia reperfusion; KATP; MAPK; Mammalian target of rapamycin; Memory; Mitochondrial ATP sensitive potassium channels; Mitogen activated protein kinases; PAT; Passive avoidance test; RIPC; ROS; Rapa; Rapamycin; Reactive Oxygen Species; Remote ischemia preconditioning; Remote ischemic preconditioning; SOD; Superoxide dismutase; mKATP; mTOR.