Pellmar T C, Hollinden G E, Sarvey J M
Physiology Department, Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5145.
Neuroscience. 1991;44(2):353-9. doi: 10.1016/0306-4522(91)90060-2.
Free radicals have been implicated in a number of pathological conditions. To evaluate the neurophysiological consequences of free radical exposure, slices of hippocampus isolated from guinea-pigs were exposed to hydrogen peroxide which reacts with tissue iron to generate hydroxyl free radicals. Long-term potentiation, a sustained increase in synaptic responses, was elicited in field CA1 by high frequency stimulation of an afferent pathway. We found that 0.002% peroxide did not directly affect the responses evoked by stimulation of the afferent pathway but did prevent maintenance of long-term potentiation. Short-term potentiation and paired-pulse facilitation were not affected by peroxide treatment. Peroxide was less effective if removed following high frequency stimulation and was ineffective if applied only after high frequency stimulation. Input/output analysis showed that the increase in synaptic efficacy was reduced with peroxide treatment. Changes in the enhanced ability of the synaptic potential to generate a spike were less apparent. These data show that the interference of free radicals with long-term potentiation may contribute to pathological deficits. It is possible that intracellular calcium regulation is disrupted by peroxide treatment. A number of second messenger systems involved with long-term potentiation are potential targets for free radical attack.
自由基与多种病理状况有关。为了评估自由基暴露对神经生理学的影响，从豚鼠分离出的海马切片被暴露于过氧化氢中，过氧化氢与组织铁反应生成羟基自由基。通过高频刺激传入通路在CA1区诱发了长时程增强，即突触反应的持续增加。我们发现，0.002%的过氧化物不会直接影响传入通路刺激所诱发的反应，但会阻止长时程增强的维持。短期增强和双脉冲易化不受过氧化物处理的影响。如果在高频刺激后去除过氧化物，其效果会减弱；如果仅在高频刺激后应用，则无效。输入/输出分析表明，过氧化物处理会降低突触效能的增加。突触电位产生动作电位的增强能力的变化不太明显。这些数据表明，自由基对长时程增强的干扰可能导致病理缺陷。过氧化物处理可能会破坏细胞内钙调节。许多与长时程增强有关的第二信使系统是自由基攻击的潜在靶点。
