Up-regulation of GABA(A) receptor binding on neurons of the prefrontal cortex in schizophrenic subjects
Up-regulation of GABA(A) receptor binding on neurons of the prefrontal cortex in schizophrenic subjects
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DOI：
10.1016/0306-4522(96)00328-4
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发表时间：
1996-12-01
期刊：
影响因子：
3.3
通讯作者：
Khan, Y
中科院分区：
文献类型：
--
作者：
Benes, FM;Vincent, SL;Khan, Y
最近的研究报告了精神分裂症受试者中间神经元密度降低和GABA增加，受体结合优先发生在前扣带皮质的第二层[Benes F.M.等人]。(1992)J.Neurosci。12,924-929]。由于在前额叶皮质的第二层也发现了中间神经元密度的减少，本研究试图确定是否在精神分裂症患者的这个区域也发现了GABA受体结合活性的上调。用高分辨率放射自显影技术分析了荷包牡丹碱敏感的[H-3]麝香酚(GABA)受体结合在第II、III、IV和VI层的单个神经元胞体上，来自正常对照组(n=16)和精神分裂症(n=7)受试者的Brodmann区10。一项计算机辅助技术已经在严格盲目的条件下被用来确定精神分裂症组中是否存在绑定方面的差异。精神分裂症组的第II、III、V、VI层GABA受体结合活性显著增强。当结合表示为相对于神经细胞大小的密度时，存在跨II、III、V和VI层的结合梯度，其中II层中的神经元胞体具有最大的颗粒密度。当分别检查根据大小标准区分的不同神经元亚群时，大(锥体)神经元显示出明显更高的结合，特别是在第二层，精神分裂症患者的结合增加了90%。小(非锥体)细胞在精神分裂症患者中的结合没有显著差异，除了第VI层，那里有135%的增加。年龄和死亡间隔的潜在混淆效应不能解释两组之间的差异，因为年轻和老年精神分裂症患者，以及死亡间隔长和短的精神分裂症患者，与以相应方式区分的对照组相比，显示出更高的GABA(A)受体结合活性。这些数据表明，精神分裂症患者可能优先减少对锥体神经元的抑制性GABA能输入，特别是在前额叶皮质的第二层。这一变化可能会导致从前额叶到精神分裂症大脑其他皮质区域的兴奋性外流增加。总体而言，这些结果与前额叶皮质GABA能活动减少可能与围产期障碍有关的观点一致，并可能是精神病病理生理学的一个潜在重要组成部分。版权所有(C)1996 IBRO。爱思唯尔科学有限公司出版。
Recent investigations have reported a reduced density of interneurons and an increase of GABA, receptor binding occurring preferentially in layer II of the anterior cingulate cortex of schizophrenic subjects [Benes F. M. et al. (1992) J. Neurosci. 12, 924-929]. Since a reduction in the density of interneurons has also been found in layer II of the prefrontal cortex, this study has sought to determine whether an up-regulation of the GABA, receptor binding activity might also be found in this region of schizophrenics. A high-resolution autoradiographic analysis of bicuculline-sensitive [H-3]muscimol (GABA,) receptor binding on individual neuron cell bodies in layers II, III, IV and VI has been applied to Brodmann area 10 from normal controls (n = 16) and schizophrenic (n = 7) subjects. A computer-assisted technique has been used under strictly blind conditions to determine whether differences in binding occur in the schizophrenic group. A significant increase of GABA, receptor binding activity has been observed in layers II, III, V and VI in the schizophrenic group. When the binding is expressed as a density with respect to neuronal cell, size, there is a gradient of binding across layers II, III, V and VI, with neuronal cell bodies in layer II having the greatest density of grains. When different subpopulations of neurons distinguished according to size criteria are examined separately, large (pyramidal) neurons show significantly higher binding, particularly in layer II, where it was increased by 90% in schizophrenics. Small (non-pyramidal) cells do not show significant differences in binding in schizophrenics, except in layer VI, where there was a 135% increase. Potential confounding effects from age and post mortem interval do not explain the differences between the two groups, because both young and old schizophrenics, as well as schizophrenics with long and short post mortem intervals, showed increased GABA(A) receptor binding activity when compared to control cases distinguished in a corresponding fashion. These data suggest that there may be a preferential reduction of inhibitory GABAergic inputs to pyramidal neurons, particularly in layer II of the prefrontal cortex, in schizophrenia. This change could potentially result in an increased excitatory outflow from the prefrontal area to other cortical regions of the schizophrenic brain.Overall, these results are consistent with the idea that reduced amounts of GABAergic activity in the prefrontal cortex could be related to a perinatal disturbance and could be a potentially important component of the pathophysiology of psychosis. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.