RESVERATROL AMELIORATES SPATIAL LEARNING MEMORY IMPAIRMENT INDUCED BY Aβ1-42 IN RATS

beta-amyloid (A beta) deposition is considered partially responsible for cognitive dysfunction in Alzheimer's disease (AD). Recently, resveratrol has been reported to play a potential role as a neuroprotective biofactor by modulating A beta pathomechanisms, including through anti-neuronal apoptotic, anti-oxidative stress, and anti-neuroinflammatory effects. In addition, SIRT1 has been demonstrated to modulate learning and memory function by regulating the expression of cAMP response binding protein (CREB), which involves in modulating the expression of SIRT1. However, whether resveratrol can alleviate An-induced cognitive dysfunction, whether SIRT1 expression and CREB phosphorylation in the hippocampus are affected by A beta, and whether resveratrol influences these effects remain unknown. In the present study, we used a hippocampal injection model in rats to investigate the effects of resveratrol on A beta(1-42)-induced impairment of spatial learning, memory and synaptic plasticity as well as on alterations of SIRT1 expression and CREB phosphorylation. We found that resveratrol significantly reversed the water maze behavioral impairment and the attenuation of long-term potentiation (LTP) in area CA1 that were induced by hippocampal injection of A beta(1-42). Interestingly, resveratrol also prevented the A beta(1-42)-induced reductions in SIRT1 expression and CREB phosphorylation in rat hippocampus. In conclusion, in rats, resveratrol protects neurons against A beta(1-42)-induced disruption of spatial learning, memory and hippocampal LTP. The mechanisms underlying the neuroprotective effects may involve rescue of SIRT1 expression and CREB phosphorylation. (C) 2016 Published by Elsevier Ltd on behalf of IBRO.