Neuroprotective effects of melatonin against anoxia/aglycemia stress, as assessed by synaptic potentials and superoxide production in rat hippocampal slices
Neuroprotective effects of melatonin against anoxia/aglycemia stress, as assessed by synaptic potentials and superoxide production in rat hippocampal slices
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DOI：
10.1111/j.1600-079x.2004.00159.x
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发表时间：
2004-11-01
影响因子：
10.3
通讯作者：
Fukuda, A
中科院分区：
文献类型：
--
作者：
Uchida, K;Samejima, M;Fukuda, A
褪黑激素在昼夜节律调节中发挥重要作用，是高效的内源性自由基清除剂和抗氧化剂。为了阐明褪黑素作为自由基清除剂的神经保护作用，我们记录了突触电位的变化，并监测了暴露于缺氧/血糖（“缺血”）应激的大鼠海马切片 CA1 锥体层中超氧化物 (O-2(.-))（使用氢乙啶）的产生。刺激谢弗侧支/连合传入神经引起的突触反应受到缺血应激的抑制。当应激持续时间为8分钟时，无论是否存在褪黑激素治疗，抑制都是可逆的，而O-2(.-)的产生量因褪黑激素的存在而减少。当应激持续时间为12分钟时，突触反应的抑制持续超过90分钟，但褪黑激素显着改善了恢复。单独缺血组在 12 分钟缺血应激后“再循环”阶段产生的 O-2(.-) 量少于褪黑素治疗组。这可能反映了具有产生 O-2(.-) 能力的活细胞数量因更严重的缺血应激而减少。其他自由基清除剂（抗坏血酸和α-生育酚）也有类似的效果。这些结果表明，褪黑激素具有通过减少 O-2(.-) 生成来保护神经元功能免受缺血性损伤的潜力。
Melatonin, which plays an important role in circadian rhythm regulation, is highly potent endogenous free radical scavenger and antioxidant. To clarify the neuroprotective effects of melatonin as a free radical scavenger, we recorded changes in synaptic potentials and monitored the generation of superoxide (O-2(.-)) (using hydroethidine) in the CA1 pyramidal layers of rat hippocampal slices exposed to anoxia/aglycemia ('ischemic') stress. Synaptic responses evoked by stimulation of Schaffer collateral/commissural afferents were suppressed by ischemic stress. When the duration of the stress was 8 min, the suppression was reversible, irrespective of the presence or absence of melatonin treatment, while the amount of O-2(.-) generated was reduced by the presence of melatonin. When stress duration was 12 min, the suppression of synaptic responses lasted more than 90 min, but melatonin significantly improved the recovery. The amount of O-2(.-) generated in the 'recirculation' phase after a 12 min ischemic stress was less in the ischemic alone group than in the melatonin-treated group. This probably reflects that the number of viable cells with the ability to generate O-2(.-) had been reduced by the more severe ischemic stress. Other radical scavengers (ascorbic acid and alpha-tocopherol) had similar effects. These results show that melatonin has the potential to protect the functions of neurons against an ischemic insult by reducing O-2(.-) generation.