Hydrogen Peroxide Modulation of Synaptic Plasticity
Hydrogen Peroxide Modulation of Synaptic Plasticity
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DOI：
10.1523/jneurosci.23-01-00269.2003
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发表时间：
2003-01
期刊：
影响因子：
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通讯作者：
A. Kamsler;M. Segal
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文献类型：
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作者：
A. Kamsler;M. Segal
与活性氧在神经退行性变中的作用不同，活性氧对突触可塑性的急性影响尚不清楚。使用大鼠海马切片，我们发现暴露于高浓度（0.5-5 mm）的 H2O2 会减少增强和非增强突触中的 EPSP。将切片暴露于 20 μmH2O2 不会影响预先建立的长期增强 (LTP) 的表达，但会阻止新的 LTP 的诱导和增强的长期抑制 (LTD)。令人惊讶的是，与对照组相比，1 μm H2O2 导致 LTP 增加两倍，并且进一步增强了不依赖于 NMDA 的 LTP。低浓度的 H2O2 也抑制了 LTD。硝苯地平是一种 L 型钙通道阻滞剂，不会影响对照 LTP，但会阻断 1 和 20 μm H2O2 的作用。钙调神经磷酸酶抑制剂 [FK506 (FR900506) 和环孢菌素 A，但不是雷帕霉素] 具有类似的作用，并且在 20 μm H2O2 存在的情况下也能恢复 LTP。这些结果表明，H2O2 通过激活钙调磷酸酶来改变不依赖于 NMDA 的电压门控钙通道介导的 LTP。
Unlike the proposed role of reactive oxygen species in neurodegeneration, acute effects of reactive oxygen on synaptic plasticity are poorly understood. Using rat hippocampal slices, we found that exposure to a high concentration (0.5–5 mm) of H2O2 reduces EPSPs in both potentiated and nonpotentiated synapses. Exposure of the slices to 20 μmH2O2 did not affect expression of preestablished long-term potentiation (LTP) but prevented induction of new LTP and enhanced long-term depression (LTD). Surprisingly, 1 μm H2O2 caused a twofold increase in LTP compared with controls, and it further enhanced NMDA-independent LTP. A low concentration of H2O2 also suppressed LTD. Nifedipine, an L-type calcium channel blocker, did not affect control LTP but blocked effects of both 1 and 20 μm H2O2. Calcineurin inhibitors [FK506 (FR900506) and cyclosporin A but not rapamycin] acted similarly and also restored LTP in the presence of 20 μm H2O2. These results suggest that H2O2 alters NMDA-independent, voltage-gated calcium channel-mediated LTP by activating calcineurin.