Waldvogel H J, Faull R L M
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Centre for Brain Research, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand; Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Adv Pharmacol. 2015;73:223-64. doi: 10.1016/bs.apha.2014.11.010. Epub 2015 Jan 17.
GABA(A) receptors are assembled into pentameric receptor complexes from a total of 19 different subunits derived from a variety of different subunit classes (α1-6, β1-3, γ1-3, δ, ɛ, θ, and π) which surround a central chloride ion channel. GABA(A) receptor complexes are distributed heterogeneously throughout the brain and spinal cord and are activated by the extensive GABAergic inhibitory system. In this chapter, we describe the heterogeneous distribution of six of the most widely distributed subunits (α1, α2, α3, β2,3, and γ2) throughout the human basal ganglia. This review describes the studies we have carried out on the normal and Huntington's disease human basal ganglia using autoradiographic labeling and immunohistochemistry in the human basal ganglia. GABA(A) receptors are known to react to changing conditions in the brain in neurological disorders, especially in Huntington's disease and display a high degree of plasticity which is thought to compensate for loss of function caused by disease. In Huntington's disease, the variable loss of GABAergic medium spiny striatopallidal projection neurons is associated with a loss of GABA(A) receptor subunits in the striosome and/or the matrix compartments of the striatum. By contrast in the globus pallidus, a loss of the GABAergic striatal projection neurons results in a dramatic upregulation of subunits on the large postsynaptic pallidal neurons; this is thought to be a compensatory plastic mechanism resulting from the loss of striatal GABAergic input. Most interestingly, our studies have revealed that the subventricular zone overlying the caudate nucleus contains a variety of proliferating progenitor stem cells that possess a heterogeneity of GABA(A) receptor subunits which may play a role in human brain repair mechanisms.
GABA(A)受体由总共19种不同亚基组装成五聚体受体复合物，这些亚基来自多种不同的亚基类别（α1 - 6、β1 - 3、γ1 - 3、δ、ɛ、θ和π），围绕着一个中央氯离子通道。GABA(A)受体复合物在整个大脑和脊髓中呈异质性分布，并由广泛的GABA能抑制系统激活。在本章中，我们描述了六种分布最广泛的亚基（α1、α2、α3、β2,3和γ2）在人类基底神经节中的异质性分布。这篇综述描述了我们在人类基底神经节中使用放射自显影标记和免疫组织化学对正常和亨廷顿病患者基底神经节所进行的研究。已知GABA(A)受体对神经系统疾病中大脑变化的状况有反应，尤其是在亨廷顿病中，并且表现出高度的可塑性，这被认为可以补偿疾病导致的功能丧失。在亨廷顿病中，GABA能中等棘状纹状体苍白球投射神经元的可变丧失与纹状体中纹状体小体和/或基质区室中GABA(A)受体亚基的丧失有关。相比之下，在苍白球中，GABA能纹状体投射神经元的丧失导致大的突触后苍白球神经元上亚基的显著上调；这被认为是由于纹状体GABA能输入丧失而产生的一种代偿性可塑性机制。最有趣的是，我们的研究表明，尾状核上方的脑室下区含有多种增殖的祖干细胞，这些细胞具有GABA(A)受体亚基的异质性，这可能在人类大脑修复机制中发挥作用。
