A neuroprotective role for polyamines in a Xenopus tadpole model of epilepsy
A neuroprotective role for polyamines in a Xenopus tadpole model of epilepsy
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DOI：
10.1038/nn.2777
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发表时间：
2011-04-01
影响因子：
25
通讯作者：
Aizenman, Carlos D.
中科院分区：
文献类型：
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作者：
Bell, Mark R.;Belarde, James A.;Aizenman, Carlos D.
多胺是参与神经损伤后细胞损伤的内源性分子，尽管目前尚不清楚多胺是否会减少或加剧这种损伤。我们使用了发育性癫痫模型，将非洲爪蟾蝌蚪暴露于戊四唑（PTZ）（一种已知的惊厥剂）中。我们发现，在初次 PTZ 暴露后，癫痫发作时间因 4 小时后第二次 PTZ 暴露而延迟。这种保护作用是腐胺（最简单的多胺）合成活性依赖性增加的结果。与直接调节离子通道的更复杂的多胺不同，腐胺通过改变兴奋与抑制的平衡来发挥其作用。初次癫痫发作 4 小时后，顶盖神经元记录显示 GABA 能自发抑制性突触后电流频率升高。我们的数据表明，这种效应是由一种非典型途径介导的，该途径将腐胺转化为 GABA，然后激活突触前 GABA(B) 受体。我们的数据表明，多胺在发育中的大脑中具有以前未知的神经保护作用。
Polyamines are endogenous molecules involved in cell damage following neurological insults, although it is unclear whether polyamines reduce or exacerbate this damage. We used a developmental seizure model in which we exposed Xenopus laevis tadpoles to pentylenetetrazole (PTZ), a known convulsant. We found that, after an initial PTZ exposure, seizure onset times were delayed in response to a second PTZ exposure 4 h later. This protective effect was a result of activity-dependent increases in synthesis of putrescine, the simplest polyamine. Unlike more complex polyamines that directly modulate ion channels, putrescine exerted its effect by altering the balance of excitation to inhibition. Tectal neuron recordings, 4 h after the initial seizure, revealed an elevated frequency of GABAergic spontaneous inhibitory postsynaptic currents. Our data suggest that this effect is mediated by an atypical pathway that converts putrescine into GABA, which then activates presynaptic GABA(B) receptors. Our data suggest that polyamines have a previously unknown neuroprotective role in the developing brain.