Publication Date:
2015-07-15
Description:
Hypoxia has been reported to cause hippocampal neurodegeneration resulting in learning and memory deficits. In the present study, we investigated the potential of salidroside, a glucoside derivative of tyrosol, in ameliorating hypoxia-induced neurodegeneration and memory impairment. Morris water maze test showed improvement in learning and spatial memory of salidroside-treated hypoxic rats correlating with increased dendritic intersections and arborization. Salidroside administration increased phosphorylation of insulin receptor subunit A (IRA) at Y972, Y1162/63 and Y1146 sites and subsequent activation of AMP-activated protein kinase (AMPK) α subunit isoforms pAMPKα1and pAMPKα2 resulting in mitochondrial biogenesis. Contrarily, silencing of IRA in salidroside supplemented hypoxic hippocampal cells could not improve cell viability or alter pAMPKα1and pAMPKα2 expression. Rats administered with salidroside showed elevated expression of phosphorylated cAMP response element-binding protein (pCREB) in the hippocampus. Salidroside administration also resulted in increased sirtuin 1 (SIRT1) activity through a cytochrome P4502E1 (CYP2E1)-regulated mechanism that was independent of pIRA. Taken together, these findings suggest a synergistic role of pIRA and SIRT1 in salidroside-mediated neuroprotection, mitochondrial biogenesis and cognitive improvement during hypoxia. This article is protected by copyright. All rights reserved.
Print ISSN:
0022-3042
Electronic ISSN:
1471-4159
Topics:
Medicine
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