Department of Psychology, Faculty of Human Sciences, Sophia University, Tokyo, Japan.
Neurosci Res. 2011 Jan;69(1):1-7. doi: 10.1016/j.neures.2010.09.004. Epub 2010 Sep 25.
Hippocampal long-term potentiation (LTP) is reportedly reduced in the presence of melatonin, but the cellular mechanisms of LTP inhibition by melatonin remain unclear. Since melatonin has the ability to scavenge free radicals such as nitric oxide (NO) and since NO has been suggested as an important contributor to LTP induction, in the present study we electrophysiologically examined whether melatonin inhibits hippocampal LTP by way of the NO signaling pathway. Field EPSP at Schaffer collateral - CA1 pyramidal cell synapses were recorded, and LTP was induced by tetanic stimulation (100 Hz, 1 s). Melatonin (100 nM) reduced the degree of LTP, and L-NAME (100 μM), an inhibitor of NO synthase, also reduced LTP, but simultaneous application of melatonin and L-NAME did not evoke any additional reduction of LTP in comparison with when only melatonin or only L-NAME were applied. Furthermore, the inhibition of LTP by the application of melatonin and L-NAME was disrupted by the application of an NO donor, DEA/NO (3 μM). The paired-pulse facilitation ratios before and after LTP induction by tetanic stimulation were nearly identical in the absence and presence of L-NAME. These results demonstrate that the inhibition of LTP in the presence of melatonin is due to the action of melatonin on the postsynaptic NO signaling pathway.
据报道，褪黑素存在时，海马长时程增强（LTP）会减少，但褪黑素抑制 LTP 的细胞机制仍不清楚。由于褪黑素具有清除自由基（如一氧化氮（NO））的能力，并且 NO 被认为是诱导 LTP 的重要因素，因此在本研究中，我们通过电生理学方法检查了褪黑素是否通过 NO 信号通路抑制海马 LTP。记录了 Schaffer 侧枝 - CA1 锥体神经元突触的场兴奋性突触后电位（field EPSP），并通过强直刺激（100 Hz，1 s）诱导 LTP。褪黑素（100 nM）降低了 LTP 的程度，NO 合酶抑制剂 L-NAME（100 μM）也降低了 LTP，但同时应用褪黑素和 L-NAME 并没有比单独应用褪黑素或 L-NAME 时引起 LTP 的额外减少。此外，应用 DEA/NO（3 μM）作为 NO 供体，破坏了褪黑素和 L-NAME 对 LTP 的抑制作用。强直刺激诱导 LTP 前后的成对脉冲易化比在没有和存在 L-NAME 的情况下几乎相同。这些结果表明，褪黑素存在时 LTP 的抑制是由于褪黑素对突触后 NO 信号通路的作用。
