期刊
JOURNAL OF NEUROCHEMISTRY
卷 135, 期 2, 页码 332-346出版社
WILEY
DOI: 10.1111/jnc.13225
关键词
hypoxia; insulin receptor; memory; mitochondrial biogenesis; salidroside; Sirtuin 1
资金
- Science and Engineering Research Board [SB/FT/LS-01/2013]
- Defence Research & Development Organization
- Ministry of Defence, Govt of India
- Department of Science & Technology, Govt of India
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) subunit isoforms pAMPK1 and pAMPK2 resulting in mitochondrial biogenesis. Contrarily, silencing of IRA in salidroside-supplemented hypoxic hippocampal cells could not improve cell viability or alter pAMPK1 and pAMPK2 expression. Rats administered with salidroside showed elevated expression of phosphorylated cAMP response element-binding protein 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.
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