Benes F M, Vincent S L, Alsterberg G, Bird E D, SanGiovanni J P
Department of Psychiatry, Harvard Medical School, Boston, Massachusetts 02115.
J Neurosci. 1992 Mar;12(3):924-9. doi: 10.1523/JNEUROSCI.12-03-00924.1992.
Recent investigations of postmortem brain from schizophrenic patients have revealed reduced numbers of neurons in several different corticolimbic brain regions. In the prefrontal and anterior cingulate cortices, more specific decreases in the numbers of interneurons, but not pyramidal cells, have been reported to occur preferentially in layer II. Based on this latter finding, a loss of inhibitory basket cells leading to a compensatory upregulation of the GABAA receptor has been hypothesized to occur in schizophrenic patients and to be a contributory factor in the pathophysiology of this disorder. We now report the results of a high-resolution quantitation of GABAA receptor binding in anterior cingulate cortex of postmortem specimens from normal and schizophrenic cases. The results indicate a preferential increase in bicuculline-sensitive 3H-muscimol binding on neuronal cell bodies of layers II and III, but not layers V and VI, of the schizophrenic cases. There was no difference in the size of neurons in any of the layers examined when the control and schizophrenic groups were compared. The neuropil of layer I also showed significantly greater GABAA binding in schizophrenics. The differences seen in the schizophrenic group did not appear to be the result of exposure to antipsychotic medication because one patient who was medication naive and a second who had received minimal exposure to antipsychotic drugs also showed elevated GABAA receptor binding. Since information processing depends on corticocortical integration in outer layers I-III, a disturbance of inhibitory activity in these superficial layers of limbic cortex may contribute to the defective associative function seen in schizophrenia.
近期对精神分裂症患者死后大脑的研究发现，几个不同的皮质边缘脑区的神经元数量减少。在前额叶和前扣带回皮质中，据报道，中间神经元数量有更特异性的减少，而非锥体细胞，这种减少优先发生在II层。基于这一发现，有人推测精神分裂症患者中抑制性篮状细胞的丧失会导致GABAA受体的代偿性上调，并且是该疾病病理生理学的一个促成因素。我们现在报告对正常和精神分裂症病例死后标本的前扣带回皮质中GABAA受体结合进行高分辨率定量的结果。结果表明，在精神分裂症病例的II层和III层神经元细胞体上，荷包牡丹碱敏感的3H-蝇蕈醇结合有优先增加，而V层和VI层则没有。当比较对照组和精神分裂症组时，在所检查的任何一层中神经元大小均无差异。I层的神经毡在精神分裂症患者中也显示出明显更高的GABAA结合。在精神分裂症组中看到的差异似乎不是接触抗精神病药物的结果，因为一名未接受过药物治疗的患者和另一名仅接受过极少抗精神病药物治疗的患者也显示出GABAA受体结合升高。由于信息处理依赖于I-III外层的皮质-皮质整合，边缘皮质这些表层抑制活性的紊乱可能导致精神分裂症中所见的关联功能缺陷。
