Resveratrol Attenuates Lipopolysaccharide-Induced Cognitive Impairments in Rats Via up Regulation of GluA1 Subunit of AMPA Receptors

Accumulating evidence suggests that synaptic dysfunction plays a major role in early Alzheimer’s disease (AD) pathogenesis prior toneuronal loss. Currently, a number of studies displays therapeutic potential of some natural products like Resveratrol. Previous studies indicate that Resveratrol by suppressing the expression of tumor necrosis factor alpha and Nuclear factor-kappa B, whereas promotingthe interleukin-10 exerts anti-inflammatory activities in pathologic conditions specially AD. The aim of the present study was to determine whether resveratrol modulates synaptic function by affecting α-amino-3- hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)receptors in the Lipopolysaccharide (LPS)-induced memory impairment as a model for AD. Materials and Methods: Neuroinflammation was induced by intracerebroventricular (ICV) injection of LPS (50μg/20μl; 10 μl per ventricle) using stereotaxic apparatus in aged male Wistar rats (n=16). A control group (n=8) only received ICV injection of the vehicle solution. The LPS-injected rats divided into model and experiment groups respectively treated with saline and Resveratrol (30mg/kg), and control rats that received saline. All the treatments were intraperitoneally, once per day, and lasted for consecutive 14 days. At the 7th day, the Y-maze test was performed to assess cognitivefunction. Moreover, on the 14th day, the animals were sacrificed, decapitated, and their hippocampus collected for further molecular assessments. The mRNA expression levels of hippocampal GluA1-4 were assessed using real-time PCR analysis. Results: The results of the Y-maze test showed that Resveratrol significantly attenuated memory damage. The mRNA level of the AMPA receptor GluA1 was decreased, while the levels of GluA2 and GluA3 were increased in the model group. There was no significant difference in GluA4 mRNA levels between control and model groups. Resveratrol could up-regulate mRNA expression of GluA1 receptor but had no effects on the other studiedreceptors. Conclusion: These findings indicate that Resveratrol may improve cognitive function in AD by regulating synaptic transmission