Minocycline cannot protect neurons against bilirubin-induced hyperexcitation in the ventral cochlear nucleus
Minocycline cannot protect neurons against bilirubin-induced hyperexcitation in the ventral cochlear nucleus
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DOI：
10.1016/j.expneurol.2012.05.017
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发表时间：
2012-09
影响因子：
5.3
通讯作者：
Chun-yan Li;Hai-Bo Shi;H. Ye;Ning-ying Song;S. Yin
中科院分区：
文献类型：
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作者：
Chun-yan Li;Hai-Bo Shi;H. Ye;Ning-ying Song;S. Yin
兴奋性毒性在许多中枢神经系统疾病中起重要作用，特别是在胆红素脑病中。米诺环素已被认为是治疗兴奋性毒性所致神经功能障碍的最有前景的潜在疗法之一。然而，一些关键问题，如米诺环素在病理条件下对神经元兴奋性和过度兴奋的电生理作用，需要澄清。本研究应用膜片钳技术，观察到胆红素对大鼠耳蜗腹核神经元自发兴奋性突触后电流(SEPSCs)和神经元放电的影响，但对sEPSCs和Glu电流的幅度无明显影响。而米诺环素对sEPSC频率和IGLU幅值无影响。此外，米诺环素预处理不能取消胆红素诱导的sEPSC增强或神经元放电。提示米诺环素不影响VCN神经元兴奋性突触传递或胆红素引起的过度兴奋。根据这些结果，我们认为米诺环素的神经保护作用，如果它能保护神经元免受胆红素等物质引起的神经毒性，则是通过另一种机制或神经元过度兴奋后的下游事件来介导的。当然，在进行进一步的临床试验之前，还需要对米诺环素的神经保护作用进行进一步的研究。
Excitotoxicity has been suggested to play an important role in many central nervous system diseases, particularly in bilirubin encephalopathy. Minocycline treatment has been proposed to be one of the most promising potential therapies for excitotoxicity-induced neurological disorders. However, some key questions, such as the electrophysiological effect of minocycline on neuronal excitability and hyperexcitation in pathological conditions, require clarification. In this study, using patch-clamp techniques, we showed that bilirubin increased the frequency of both spontaneous excitatory postsynaptic currents (sEPSCs) and neuronal firing in isolated ventral cochlear nucleus (VCN) neurons at postnatal days 11–14 (P11–14) in rats but it did not affect the amplitude of sEPSCs or glutamate-activated (IGlu) currents. However, minocycline had no effect on sEPSC frequency or IGluamplitude. Furthermore, minocycline pretreatment did not abolish bilirubin-induced sEPSC potentiation or neuron firing. These data suggest that minocycline does not affect excitatory synaptic transmission or hyperexcitation induced by bilirubin in VCN neurons. From these results, we propose that the neuroprotective efficacy of minocycline, if it can protect neurons against neurotoxicity induced by substances like bilirubin, is mediated by either an alternative mechanism or downstream events post neuronal hyperexcitation. Certainly, additional investigation of the neuroprotective effects of minocycline is required before embarking on further clinical trials.