| Objective: Resveratrol is a naturally occurring phytoalexin, mainly present in grapes and red wine, with important biological properties. Recent studies indicate that resveratrol has a neuroprotective effect in various models, such as protects the cultured hippocampal neurons against neurotoxicity induced by beta-amyloid peptide and nitric oxide (NO); upregulates NO in spinal cord and protect spinal cord from ischemia-reperfusion injury in New Zealand white rabbits. Recently, we found that resveratrol shortened the duration of action potential in papillary muscles in normal guinea pig and also decreased the maximal velocity of phase 0 depolarization in partially depolarized papillary muscles. These effects were likely due to a decrease in calcium influx. However, the effect of resveratrol on the electrical activity of neurons of the rat hippocampus has not been reported. Therefore, this study was designed to examine the effect of resveratrol on the electrical activity of neurons of the rat hippocampus in slice preparation using extracellular recording technique. Methods: All experiments were performed on CA1 pyramidal cells of hippocampal slices prepared from male Sprague-Dawley rats (21±3d). Rats were rapidly decapitated, the forebrains were removed and placed into a dish with ice-cold oxygenated artificial cerebrospinal fluid (ACSF). The hippocampus was dissected and then sliced (thickness of 350-500 μm). The slices were preincubated in ACSF aerated with 95% O2 and 5% CO2 for 60 -90 min at room temperature before recording, then the effects of resveratrol on the discharges of neurons in CA1 area of rat hippocampal slices were examined by using extracellular recording technique. Results: (1) In response to the application of resveratrol (0.05, 0.5, 5 μmol/L, n=52) into the superfusate for 2 min, the spontaneous discharge rate of 46/52 (88.5%) neurons was significantly decreased in a dose-dependent manner; (2) Application of L-glutamate (0.2 mmol/L) into the superfusate led to a marked increase in discharge rate of all 8 (100%) neurons in an epileptiform pattern. The increased discharges of all 8 (100%) neurons were suppressed by application of resveratrol (5 μmol/L); (3) In 7 slices, perfusion of the selective L-type calcium channel agonist, Bay K8644 (0.1 μmol/L), induced a significant increase in the discharge rate of 6/7 (85.7%) neurons. The increased discharges of all 6/6 (100%) neurons were suppressed by application of resveratrol (5 μmol/L); (4) In 9 slices, perfusion of nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 50 μmol/L) into the superfusate significantly augmented the discharge rate of 7/9 (77.8%) neurons. Resveratrol (5 μmol/L) applied into the superfusate reduced the increased discharges ofall 7/7 (100%) neurons; (5) In 10 units, the large-conductance Ca2+-activied K+ channel blocker (tetraethylammonium chloride, TEA, 1mmol/L) significantly increased the discharge rate of 9/10 (90%) neurons. Resveratrol (5 μmol/L) applied into the superfusate inhibited the discharges of 8/9 (88.9%) neurons. Conclusion: These results suggest that resveratrol inhibits the electrical activity of hippocampal CA1 neurons. This effect may be related to its properties of blockade of L-type voltage-gated calcium channel and NO promoting, and probably has no association with large-conductance Ca2+-activied K+ channel. ⅡEffects of resveratrol on the electrical activity of subfornical organ neurons in rat Objective: Over the past several years, a large body of evidence has suggested that resveratrol has a neuroprotective effect in various models, such as protects the cultured hippocampal neurons against neurotoxicity induced by beta-amyloid peptide and nitric oxide (NO), and protects thecentral nervous system (CNS) against global ischemic injury in gerbils . Furthermore, study by Gupta et al also demonstrated that resveratrol can significantly attenuate seizures induced by kainic acid in rat. The subfornical organ (SFO) is one of the circumventricular organs (CVOs), locat... |
