Molecular Neuroscience, Institute of Life Science, School of Medicine, Swansea University Swansea, UK.
Front Mol Neurosci. 2009 Nov 4;2:25. doi: 10.3389/neuro.02.025.2009. eCollection 2009.
Inhibitory neurotransmitter receptors for glycine (GlyR) are heteropentameric chloride ion channels that are comprised of four functional subunits, alpha1-3 and beta and that facilitate fast-response, inhibitory neurotransmission in the mammalian brain and spinal cord. We have investigated the distribution of GlyRs in the human forebrain, brainstem, and cervical spinal cord using immunohistochemistry at light and confocal laser scanning microscopy levels. This review will summarize the present knowledge on the GlyR distribution in the human brain using our established immunohistochemical techniques. The results of our immunohistochemical labeling studies demonstrated GlyR immunoreactivity (IR) throughout the human basal ganglia, substantia nigra, various pontine regions, rostral medulla oblongata and the cervical spinal cord present an intense and abundant punctate IR along the membranes of the neuronal soma and dendrites. This work is part of a systematic study of inhibitory neurotransmitter receptor distribution in the human CNS, and provides a basis for additional detailed physiological and pharmacological studies on the inter-relationship of GlyR, GABA(A)R and gephyrin in the human brain. This basic mapping exercise, we believe, will provide important baselines for the testing of future pharmacotherapies and drug regimes that modulate neuroinhibitory systems. These findings provide new information for understanding the complexity of glycinergic functions in the human brain, which will translate into the contribution of inhibitory mechanisms in paroxysmal disorders and neurodegenerative diseases such as Epilepsy, Huntington's and Parkinson's Disease and Motor Neuron Disease.
甘氨酸(Glycine)抑制性神经递质受体是由四个功能亚基(alpha1-3 和 beta)组成的异戊二烯氯离通道,促进哺乳动物大脑和脊髓中的快速反应抑制性神经传递。我们使用免疫组织化学和共聚焦激光扫描显微镜技术在光镜和共聚焦激光扫描显微镜水平上研究了 GlyRs 在人脑中的分布。这篇综述将总结我们使用已建立的免疫组织化学技术在人脑 GlyR 分布方面的现有知识。我们的免疫组织化学标记研究结果表明,GlyR 免疫反应(IR)存在于整个基底神经节、黑质、各种脑桥区域、延髓头部和颈段脊髓中,神经元胞体和树突膜上存在强烈而丰富的点状 IR。这项工作是对人类中枢神经系统抑制性神经递质受体分布的系统研究的一部分,为进一步研究 GlyR、GABA(A)R 和 gephyrin 之间在人类大脑中的相互关系的生理学和药理学研究提供了基础。我们认为,这种基本的映射练习将为未来调节神经抑制系统的药物治疗和药物方案的测试提供重要的基线。这些发现为理解人类大脑中甘氨酸能功能的复杂性提供了新的信息,这将有助于理解阵发性疾病和神经退行性疾病(如癫痫、亨廷顿氏病和帕金森氏病以及运动神经元病)中抑制机制的作用。