A change in the density of [3H]flumazenil, but not [3H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder
A change in the density of [3H]flumazenil, but not [3H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder
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DOI：
10.1016/s0165-0327(00)00294-9
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发表时间：
2001-10-01
影响因子：
6.6
通讯作者：
Copolov, D
中科院分区：
文献类型：
--
作者：
Dean, B;Pavey, G;Copolov, D
背景：本研究检验了皮质血清素能发生变化的假设。双相情感障碍和精神分裂症中的 GABA 能和谷氨酸能系统。方法：使用原位放射性配体结合和放射自显影术测量对照受试者和双相情感障碍或精神分裂症受试者（每组 n = 8）布罗德曼区（BA）9 的神经化学标记物。结果：与精神分裂症患者（平均 +/-S.E.M. 385 +/- 44 fmol/mg ETE）和对照（383 +/- 44 fmol/mg ETE）受试者的组织相比，双相情感障碍受试者中 [H-3] 氟马西尼与 GABA 受体上苯二氮卓结合位点的结合密度增加（451 +/- 17 fmol/mg ETE；P < 0.05）。三组之间的 [H-3] 蝇蕈醇与 GABA(A) 受体结合的密度或血清素 (1A) 受体、血清素 (2A) 受体、离子型谷氨酸受体或血清素转运蛋白的密度没有差异。对照组受试者的 NMDA 受体密度随年龄增长而下降，而精神分裂症和双相情感障碍则不存在这一现象。在精神分裂症患者和双相情感障碍患者中，[H-3]氟马西尼结合不存在与年龄相关的增加。局限性：本研究涉及的个体数量相对较少。结论：GABA(A) 受体中 γ2 受体亚基的增加已被证明会增加苯二氮卓类药物的结合，但不会增加 [H-3] 蝇蕈醇的结合，这是我们在双相情感障碍受试者的 BA 9 中显示的结合不匹配。因此，受体亚基组装成 GABA(A) 受体的变化可能与双相情感障碍的神经病理学有关。双相情感障碍和精神分裂症之间的皮质受体密度与年龄相关的变化也可能存在差异。 (C) 2001 Elsevier Science B.V. 保留所有权利。
Background: This study examines the hypothesis that there are changes in cortical serotonergic. GABAergic and glutumatergic systems in bipolar disorder and schizophrenia. Methods: In situ radioligand binding and autoradiography were used to measure neurochemical markers in Brodmann's Area (BA) 9 from control subjects and subjects with bipolar disorder or schizophrenia (n = 8 per group). Results: Compared to tissue from schizophrenic (mean +/-S.E.M. 385 +/- 44 fmol/mg ETE) and control (383 +/- 44 fmol/mg ETE) subjects, there was an increase in the density of [H-3]flumazenil binding to the benzodiazepine binding site on the GABA, receptor in subjects with bipolar disorder (451 +/- 17 fmol/mg ETE; P < 0.05). There was no difference in the density of [H-3]muscimol binding to the GABA(A) receptor or in the density of the serotonin(1A) receptor, serotonin(2A) receptor, ionotropic glutamate receptors or the serotonin transporter between the three cohorts. There was an age-related decrease in NMDA receptor density in control subjects that was absent in schizophrenia and bipolar disorder. An age-related increase in [H-3]flumazenil binding in schizophrenia was absent in control and bipolar disorder subjects. Limitations: This Study involved a relatively small number of individuals. Conclusions: An increase in the gamma2-receptor sub-unit in the GABA(A) receptor has been shown to increase benzodiazepine but not [H-3]muscimol binding, this is the mismatch in binding we have shown in BA 9 from subjects with bipolar disorder. Thus, a change in the assembly of receptor subunits into GABA(A), receptors may be involved in the neuropathology of bipolar disorder. There may also be differences in age-related changes in cortical receptor density between bipolar disorder and schizophrenia. (C) 2001 Elsevier Science B.V. All rights reserved.