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首页> 外文期刊>The European Journal of Neuroscience >Differential expression of GABA and glycine receptors in ALS-resistant vs. ALS-vulnerable motoneurons: possible implications for selective vulnerability of motoneurons.
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Differential expression of GABA and glycine receptors in ALS-resistant vs. ALS-vulnerable motoneurons: possible implications for selective vulnerability of motoneurons.

机译：ALS抵抗性和ALS易受伤害的运动神经元中GABA和甘氨酸受体的差异表达：对运动神经元选择性脆弱性的可能影响。

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Summary Amyotrophic lateral sclerosis (ALS) is a devastating motoneuronal degenerative disease, which is inevitably fatal in adults. ALS is characterized by an extensive loss of motoneurons in the cerebrospinal axis, except for those motoneurons that control eye movements and bladder contraction. The reason for this selectivity is not known. Systematic differences have been found in the organization of excitatory synaptic transmission in ALS-resistant vs. ALS-susceptible motor nuclei. However, although motoneurons express high levels of glycine receptors (GlyR) and GABA(A) receptors (GABA(A)R), no such studies have been carried out yet for inhibitory synaptic transmission. In this study, we compared the subunit composition, patterns of expression, density and synaptic localization of inhibitory synaptic receptors in ALS-resistant (oculomotor, trochlear and abducens) and ALS-vulnerable motoneurons (trigeminal, facial and hypoglossi). Triple immunofluorescent stainings of the major GABA(A)R subunits (alpha1, alpha2, alpha3, and alpha5), the GlyR alpha1 subunit and gephyrin, were visualized by confocal microscopy and analysed quantitatively. A strong correlation was observed between the vulnerability of motoneurons and the subunit composition of GABA(A)R, the GlyR/GABA(A)R density ratios and the incidence of synaptic vs. extrasynaptic GABA(A)R. These differences contrast strikingly with the uniform gephyrin cluster density and synaptic GlyR levels recorded in all motor nuclei examined. These results suggest that the specific patterns of inhibitory receptor organization observed might reflect functional differences that are relevant to the physiopathology of ALS.
机译：总结肌萎缩性侧索硬化症（ALS）是毁灭性的运动神经元变性疾病，在成人中不可避免地致命。 ALS的特征是除了控制眼球运动和膀胱收缩的运动神经元外，运动神经元在脑脊髓轴上大量丢失。这种选择性的原因尚不清楚。在ALS抵抗性和ALS易感性运动核的兴奋性突触传递组织中发现了系统性差异。但是，尽管运动神经元表达高水平的甘氨酸受体（GlyR）和GABA（A）受体（GABA（A）R），但尚未进行抑制突触传递的此类研究。在这项研究中，我们比较了在ALS耐药（动眼，滑车和外展肌）和ALS易受伤害的运动神经元（三叉神经，面部和视神经减退）中抑制性突触受体的亚基组成，表达方式，密度和突触定位。通过共聚焦显微镜观察主要GABA（A）R亚基（alpha1，alpha2，alpha3和alpha5），GlyR alpha1亚基和gephyrin的三重免疫荧光染色，并进行定量分析。观察到运动神经元的脆弱性与GABA（A）R的亚基组成，GlyR / GABA（A）R的密度比以及突触与突触外GABA（A）R的发生之间有很强的相关性。这些差异与在所有检查的运动核中记录的均匀gephyrin簇密度和突触GlyR水平形成鲜明对比。这些结果表明，观察到的抑制性受体组织的特定模式可能反映了与ALS生理病理学相关的功能差异。

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