The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat.

The effect of bilirubin on the excitability of mitral cells in the olfactory bulb of the rat.
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胆红素对大鼠嗅球二尖瓣细胞兴奋性的影响

DOI:
10.1038/srep32872
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发表时间:
2016-09-09
期刊:
影响因子:
4.6
通讯作者:
Zhang WT
Zhang WT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen XJ;Zhou HQ;Ye HB;Li CY;Zhang WT

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嗅觉功能障碍是各种肝病常见的临床现象。以前的研究表明,肝病患者的嗅觉障碍与胆红素水平之间存在相关性。胆红素是一种众所周知的神经毒素;然而,它对嗅觉系统中第一个中继器--主嗅球(MOB)神经元的影响尚未得到研究。我们研究了胆红素(>3 μM)对MOB的主要输出神经元--二尖瓣细胞的影响。胆红素可增加自发放电频率和自发兴奋性突触后电流(SEPSCs)的频率,但不增加其幅度。TTX完全阻断了几乎所有被测试细胞中的sEPSCs。N-甲基-D-天冬氨酸和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体拮抗剂可部分阻断胆红素活性。此外,我们还发现胆红素增加了MC内不依赖突触传递的固有放电频率。我们的发现表明,胆红素增强谷氨酸能传递和增强不依赖突触传递的固有放电,所有这些都导致MC的过度兴奋。我们的发现为进一步研究在严重肝病患者中经常观察到的嗅觉障碍的机制提供了基础。
Olfactory dysfunction is a common clinical phenomenon observed in various liver diseases. Previous studies have shown a correlation between smell disorders and bilirubin levels in patients with hepatic diseases. Bilirubin is a well-known neurotoxin; however, its effect on neurons in the main olfactory bulb (MOB), the first relay in the olfactory system, has not been examined. We investigated the effect of bilirubin (>3 μM) on mitral cells (MCs), the principal output neurons of the MOB. Bilirubin increased the frequency of spontaneous firing and the frequency but not the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). TTX completely blocked sEPSCs in almost all of the cells tested. Bilirubin activity was partially blocked by N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepro pionic acid (AMPA) receptor antagonists. Furthermore, we found that bilirubin increased the frequency of intrinsic firing independent of synaptic transmission in MCs. Our findings suggest that bilirubin enhances glutamatergic transmission and strengthens intrinsic firing independent of synaptic transmission, all of which cause hyperexcitability in MCs. Our findings provide the basis for further investigation into the mechanisms underlying olfactory dysfunction that are often observed in patients with severe liver disease.
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