Benes F M, Todtenkopf M S, Logiotatos P, Williams M
Laboratory of Structural Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA 02178, USA.
J Chem Neuroanat. 2000 Dec;20(3-4):259-69. doi: 10.1016/s0891-0618(00)00105-8.
Recent postmortem studies have been suggesting that a defect of GABAergic neurotransmission might occur in the corticolimbic system of subjects with schizophrenia and bipolar disorder. To explore this possibility, a method for immunolocalizing the 65 kdalton isoform of glutamate decarboxylase (GAD(65)) has been developed and applied to the anterior cingulate (ACCx) and prefrontal (PFCx) cortices of 12 normal controls (CONs), 12 schizophrenics (SZs) and 5 manic depressive (MDs) subjects. A computer-assisted technique was employed under strictly blind conditions to determine the density of GAD(65)-IR terminals in apposition with pyramidal (PNs) and nonpyramidal (NPs) neurons and in neuropil (NPL) of layers II, III, V and VI of each cortical region. For SZs, no difference in the numerical density of GAD(65)-IR terminals in contact with either PNs or NPs or in NPL of layers II-VI in ACCx or PFCx was detected. There were also no differences in the size of either PNs and NPs that could have influenced the nature of these findings. Using a pixel count analysis, the size of IR terminals was, however, found to be increased in layers II (10.3%) and III (15.8%) of SZs, but only in subjects treated with neuroleptic drugs. For MDs, the density of GAD(65)-IR terminals was significantly reduced in all four layers of ACCx, but these differences were most significant in layers II (27.8%) and III (37.2%), whether or not the subjected were treated with neuroleptics. In PFCx, the MDs showed similar differences in terminal density for PNs and NPs but not neuropil in the four laminae examined. The MD group showed no differences in either the size of cell bodies or IR terminals. Age and PMI did not account for any of the differences between the CONs vs SZs and MDs. Overall, the results of this study, though preliminary, suggest that there may be complex changes in GABAergic terminals in SZ and MD, ones that may vary with respect to primary diagnosis and neuroleptic exposure.
最近的尸检研究表明，精神分裂症和双相情感障碍患者的皮质边缘系统可能存在γ-氨基丁酸能神经传递缺陷。为了探究这种可能性，已开发出一种对65千道尔顿谷氨酸脱羧酶（GAD(65)）亚型进行免疫定位的方法，并将其应用于12名正常对照者（CONs）、12名精神分裂症患者（SZs）和5名躁郁症（MDs）患者的前扣带回（ACCx）和前额叶（PFCx）皮质。在严格的盲法条件下采用计算机辅助技术，以确定GAD(65)免疫反应性终末与锥体神经元（PNs）和非锥体神经元（NPs）以及每个皮质区域II、III、V和VI层神经毡（NPL）相邻处的密度。对于SZs，未检测到ACCx或PFCx中与PNs或NPs接触的GAD(65)免疫反应性终末的数值密度或II - VI层NPL中的数值密度有差异。PNs和NPs的大小也没有差异，而这可能会影响这些研究结果的性质。然而，通过像素计数分析发现，仅在接受抗精神病药物治疗的SZs患者中，II层（10.3%）和III层（15.8%）的免疫反应性终末大小增加。对于MDs，ACCx所有四层中GAD(65)免疫反应性终末的密度均显著降低，但无论患者是否接受抗精神病药物治疗，这些差异在II层（27.8%）和III层（37.2%）最为显著。在PFCx中，MDs在检查的四个层中，PNs和NPs的终末密度存在类似差异，但神经毡无差异。MD组在细胞体大小或免疫反应性终末大小方面均无差异。年龄和死后间隔时间不能解释CONs与SZs和MDs之间的任何差异。总体而言，本研究结果虽然初步，但表明SZ和MD中γ-氨基丁酸能终末可能存在复杂变化，这些变化可能因初步诊断和抗精神病药物暴露情况而异。
