Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism.
Decreased GABAA receptors and benzodiazepine binding sites in the anterior cingulate cortex in autism.
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DOI：
10.1002/aur.88
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发表时间：
2009-08
期刊：
影响因子：
4.7
通讯作者：
Blatt, G. J.
中科院分区：
文献类型：
--
作者：
Oblak, A.;Gibbs, T. T.;Blatt, G. J.
前扣带皮层 (ACC; BA 24) 通过其广泛的边缘和高阶关联皮层与前额叶皮层的连接，是参与执行功能、情感和社会情感行为的重要回路的关键部分。包括遗传和影像学研究在内的多种证据表明 ACC 和 GABA 系统可能在自闭症中受到影响。 GABAA 受体复合物上的苯二氮卓结合位点是药物治疗的重要靶点，具有重要的临床意义。目前的多浓度配体结合研究利用 3H-蝇蕈醇和 3H-氟硝西泮分别测定成人自闭症患者和对照病例 ACC 中 GABAA 受体和苯二氮卓结合位点的数量 (Bmax)、结合亲和力 (Kd) 和分布。与对照组相比，自闭症组 ACC 颗粒上层 (46.8%) 和颗粒下层 (20.2%) 的 GABAA 受体平均密度以及颗粒上层 (28.9%) 和颗粒下层 (16.4%) 中苯二氮卓结合位点的密度显着降低。此外，自闭症组的颗粒下层（17.1%）中发现苯二氮卓位点密度有下降的趋势。这些发现表明，在自闭症组中，ACC 中苯二氮卓类位点和 GABAA 受体的下调可能是由于 GABA 神经支配和/或释放增加，扰乱了主要神经元微妙的兴奋/抑制平衡及其对关键边缘皮质目标的输出。这种干扰可能是自闭症社会情感行为核心改变的基础。
The anterior cingulate cortex (ACC; BA 24) via its extensive limbic and high order association cortical connectivity to prefrontal cortex is a key part of an important circuitry participating in executive function, affect, and socio-emotional behavior. Multiple lines of evidence, including genetic and imaging studies, suggest that the ACC and GABA system may be affected in autism. The benzodiazepine binding site on the GABAA receptor complex is an important target for pharmacotherapy and has important clinical implications. The present multiple-concentration ligand-binding study utilized 3H-muscimol and 3H-flunitrazepam to determine the number (Bmax), binding affinity (Kd), and distribution of GABAA receptors and benzodiazepine binding sites, respectively, in the ACC in adult autistic and control cases. Compared to controls, the autistic group had significant decreases in the mean density of GABAA receptors in the supragranular (46.8%) and infragranular (20.2%) layers of the ACC and in the density of benzodiazepine binding sites in the supragranular (28.9%) and infragranular (16.4 %) lamina. In addition, a trend for a decrease in for the density of benzodiazepine sites was found in the infragranular layers (17.1%) in the autism group. These findings suggest that in the autistic group this downregulation of both benzodiazepine sites and GABAA receptors in the ACC may be the result of increased GABA innervation and/or release disturbing the delicate excitation/inhibition balance of principal neurons as well as their output to key limbic cortical targets. Such disturbances likely underlie the core alterations in socio-emotional behaviors in autism.
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