Inhibition of excitatory synaptic transmission by trans-resveratrol in rat hippocampus

The red wine polyphenol trans-resveratrol has been found to exert potent protective actions in a variety of cerebral ischemia models. The neuroprotection by trans-resveratrol thus far is mainly attributed to its intrinsic antioxidant properties. In the present study, the effects of the red wine polyphenol on excitatory synaptic transmission were investigated in the CA1 region of rat hippocampal slices. Perfusion with trans-resveratrol (10–100 μM) caused a concentration-dependent inhibition on the filed excitatory postsynaptic potentials (the field EPSPs) without detectable effect on the presynaptic volleys. The inhibition had a slow onset and was reversible. Trans-resveratrol (30 μM) did not change the ratios of paired-pulse facilitation of the field EPSPs tested at intervals of 20, 40 and 80 ms, nor did it alter the membrane properties of postsynaptic CA1 pyramidal neurons. However, trans-resveratrol (30 μM) significantly suppressed glutamate-induced currents in postsynaptic CA1 pyramidal neurons. In dissociated hippocampal neurons, the IC50 value of trans-resveratrol in inhibition of glutamate-induced currents was 53.3 ± 9.4 μM. Kainite and NMDA receptors were more sensitive to the red wine polyphenol than AMPA receptors. The present study for the first time demonstrates that trans-resveratrol inhibits the postsynaptic glutamate receptors, which probably works in concert with its antioxidant action for ameliorating the brain ischemic injury. The findings also support the future use of trans-resveratrol in the treatment of various neurodegenerative disorders.