Benes F M, Vincent S L, Marie A, Khan Y
Laboratory for Structural Neuroscience, McLean Hospital, Belmont, MA 02178, USA.
Neuroscience. 1996 Dec;75(4):1021-31. doi: 10.1016/0306-4522(96)00328-4.
Recent investigations have reported a reduced density of interneurons and an increase of GABAA 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 un-regulation of the GABAA receptor binding activity might also be found in this region of schizophrenics. A high-resolution autoradiographic analysis of bicuculline-sensitive [3H]muscimol (GABAA) 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 GABAA 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 GABAA 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 preferential 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.
近期研究报告称，精神分裂症患者前扣带回皮质II层的中间神经元密度降低，且GABAA受体结合增加[贝内斯F.M.等人（1992年）《神经科学杂志》12卷，924 - 929页]。由于前额叶皮质II层也发现中间神经元密度降低，本研究旨在确定精神分裂症患者的该区域是否也存在GABAA受体结合活性失调。对正常对照组（n = 16）和精神分裂症患者（n = 7）的布罗德曼10区II、III、IV和VI层单个神经元细胞体上荷包牡丹碱敏感的[3H]蝇蕈醇（GABAA）受体结合进行了高分辨率放射自显影分析。在严格的盲法条件下使用计算机辅助技术来确定精神分裂症组中结合是否存在差异。在精神分裂症组的II、III、V和VI层观察到GABAA受体结合活性显著增加。当结合以相对于神经元细胞大小的密度表示时，II、III、V和VI层存在结合梯度，II层的神经元细胞体具有最高的颗粒密度。当根据大小标准区分的不同神经元亚群分别进行检查时，大（锥体）神经元显示出显著更高的结合，特别是在II层，精神分裂症患者中该层的结合增加了90%。小（非锥体）细胞在精神分裂症患者中结合无显著差异，除了VI层，该层增加了135%。年龄和死后间隔的潜在混杂效应无法解释两组之间的差异，因为与以相应方式区分的对照病例相比，年轻和老年精神分裂症患者以及死后间隔长和短的精神分裂症患者均显示GABAA受体结合活性增加。这些数据表明，在精神分裂症中，可能存在对锥体神经元抑制性GABA能输入的优先减少，特别是在前额叶皮质的II层。这种变化可能潜在地导致精神分裂症患者前额叶区域向其他皮质区域的兴奋性输出增加。总体而言，这些结果与以下观点一致，即前额叶皮质中GABA能活性降低可能与围产期紊乱有关，并且可能是精神病病理生理学的一个潜在重要组成部分。
