Department of Otorhinolaryngology-Head &Neck Surgery Affiliated Sixth People's Hospital of Shanghai Jiaotong University, Shanghai, P.R. China.
Sci Rep. 2016 Sep 9;6:32872. doi: 10.1038/srep32872.
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.
嗅觉功能障碍是各种肝脏疾病中常见的临床现象。先前的研究表明，嗅觉障碍与肝病患者的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，它对嗅球（olfactory bulb，MOB）中神经元的影响尚未被研究。MOB 是嗅觉系统的第一级中继站，我们研究了胆红素（>3μM）对嗅球中主细胞（mitral cells，MCs）的影响，MCs 是 MOB 的主要输出神经元。胆红素增加了自发放电的频率和自发性兴奋性突触后电流（spontaneous excitatory postsynaptic currents，sEPSCs）的频率，但不增加其幅度。TTX 几乎完全阻断了所有测试细胞中的 sEPSCs。NMDA 和 AMPA 受体拮抗剂部分阻断了胆红素的活性。此外，我们发现胆红素增加了 MCs 中独立于突触传递的内在放电频率。我们的发现表明，胆红素增强了谷氨酸能传递，并增强了独立于突触传递的内在放电，所有这些都会导致 MCs 的过度兴奋。我们的发现为进一步研究严重肝病患者中经常观察到的嗅觉功能障碍的机制提供了基础。
