Taurine protects against bilirubin-induced hyperexcitation in rat anteroventral cochlear nucleus neurons
Taurine protects against bilirubin-induced hyperexcitation in rat anteroventral cochlear nucleus neurons
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牛磺酸保护大鼠耳蜗前腹核神经元免受胆红素诱导的过度兴奋
DOI：
10.1016/j.expneurol.2013.12.014
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发表时间：
2014-04
影响因子：
5.3
通讯作者：
Shan-kai Yin
中科院分区：
文献类型：
--
作者：
Min Liang;Hai-bo Shi;Guo-ying Han;Shan-kai Yin
目前还没有有效的治疗高胆红素血症的药物。牛磺酸被认为具有神经保护作用。本研究的目的是确定牛磺酸是否保护大鼠前腹侧耳蜗核（AVCN）神经元对胆红素诱导的神经元过度兴奋。AVCN神经元分离自13至15日龄的Sprague-Dawley大鼠。比较胆红素与牛磺酸联合作用对自发兴奋性突触后电流（sEPSC）和动作电位电流的影响。胆红素显著增加sEPSC的频率和动作电位电流，但不增加sEPSC的振幅。牛磺酸以剂量依赖性方式抑制胆红素引起的动作电位频率增加。此外，牛磺酸降低了电压依赖性钙通道电流的幅度，增加胆红素。我们分别用GABA A和甘氨酸受体拮抗剂荷包牡丹碱和士的宁探讨了牛磺酸的保护作用机制。加入荷包牡丹碱和士的宁可消除牛磺酸的保护作用。胆红素和牛磺酸均不影响谷氨酸受体的敏感性。因此，我们的研究结果表明，牛磺酸保护AVCN神经元对胆红素诱导的神经元过度兴奋激活GABA和甘氨酸受体，抑制钙流通过电压门控通道。因此，牛磺酸可能是治疗新生儿高胆红素血症的有效药物。
No effective medication for hyperbilirubinemia yet exists. Taurine is believed to exert a neuroprotective action. The aim of the present study was to determine whether taurine protected neurons of the rat anteroventral cochlear nucleus (AVCN) against bilirubin-induced neuronal hyperexcitation. AVCN neurons were isolated from 13 to 15-day-old Sprague–Dawley rats. The effects of bilirubin on the spontaneous excitatory postsynaptic currents (sEPSCs) and action potential currents were compared with those exerted by bilirubin and taurine together. Bilirubin dramatically increased the frequencies of sEPSCs and action potential currents, but not sEPSC amplitude. Taurine suppressed the enhanced frequency of action potentials induced by bilirubin, in a dose-dependent manner. In addition, taurine decreased the amplitude of voltage-dependent calcium channel currents that were enhanced upon addition of bilirubin. We explored the mechanism of the protective effects exerted by taurine using GABAAand glycine receptor antagonists, bicuculline and strychnine, respectively. Addition of bicuculline and strychnine eliminated the protective effects of taurine. Neither bilirubin nor taurine affected the sensitivity of the glutamate receptor. Our findings thus indicate that taurine protected AVCN neurons against bilirubin-induced neuronal hyperexcitation by activating the GABAAand glycine receptors and inhibiting calcium flow through voltage-gated channels. Thus, taurine may be effective in treatment of neonatal hyperbilirubinemia.
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