We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Insulin receptor A and Sirtuin 1 synergistically improve learning and spatial memory following chronic salidroside treatment during hypoxia.
- Authors
Barhwal, Kalpana; Das, Saroj K.; Kumar, Ashish; Hota, Sunil K.; Srivastava, Ravi B.
- Abstract
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 pAMPKα1 and pAMPKα2 resulting in mitochondrial biogenesis. Contrarily, silencing of IRA in salidroside-supplemented hypoxic hippocampal cells could not improve cell viability or alter pAMPKα1 and pAMPKα2 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.
- Subjects
HYPOXEMIA; INSULIN receptors; MITOCHONDRIAL membranes; ORIGIN of life; SIRTUINS
- Publication
Journal of Neurochemistry, 2015, Vol 135, Issue 2, p332
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.13225