Alterations in GABAergic biomarkers in the autism brain: research findings and clinical implications.
Alterations in GABAergic biomarkers in the autism brain: research findings and clinical implications.
复制标题
DOI：
10.1002/ar.21252
复制
发表时间：
2011-10
影响因子：
2
通讯作者：
Fatemi, S. Hossein
中科院分区：
文献类型：
--
作者：
Blatt, Gene J.;Fatemi, S. Hossein
自闭症是一种广泛性的发育障碍，其特征是重复的刻板行为，社交情感缺陷和延迟或缺乏语言能力。有已知的神经病理学在自闭症大脑影响边缘系统，小脑和皮质结构，但受影响的个人，在死后组织研究中发现的神经化学概况，只是最近才出现。在自闭症中受到高度影响的一个主要组成部分是GABA能系统。现在很明显，有广泛的显着影响，在许多分布在自闭症大脑的组织化学，放射自显影和生化研究揭示的区域。GABA的关键合成酶，谷氨酸脱羧酶65型和67型（GAD65，GAD67），在小脑和mRNA水平的仔细检查显示，这在很大程度上是由于减少浦肯野细胞和一个亚群的较大的齿状神经元原位杂交研究所测量的。其他细胞类型的GAD水平正常（高尔基体细胞，较小的齿状中间神经元和星状细胞）或水平增加（篮状细胞）。GABA受体密度、数量和蛋白表达在小脑和选择的皮质区域都降低。GABAA和GABAB亚基蛋白表达在小脑、BA 9和BA 40中显著降低。海马和前扣带皮层（BA 24）中的苯二氮卓类结合位点显著减少。总之，来自这些研究的数据表明，自闭症大脑中的抑制性GABA系统存在明显的失调，影响定位于特定细胞类型的特定生物标志物和可能影响电路和行为的薄层。
Autism is a pervasive developmental disorder characterized by repetitive stereotyped behavior, social-emotional deficits and delayed or absent language abilities. There are known neuropathologies in the autism brain affecting limbic, cerebellar and cortical structures but the neurochemical profile of affected individuals, revealed in postmortem tissue studies, is only recently emerging. One major component that appears highly impacted in autism is the GABAergic system. It is now apparent that there are widespread significant effects in many distributed regions in the autism brain revealed by histochemical, autoradiographic and biochemical studies. The key synthesizing enzymes for GABA, glutamic acid decarboxylase type 65 and 67 (GAD65, GAD67), are decreased in the cerebellum and closer examination of mRNA levels revealed that it is largely due to decreases in Purkinje cells and a subpopulation of larger dentate neurons as measured by in situ hybridization studies. Other cell types had either normal GAD levels (Golgi cells, smaller dentate interneurons and stellate cells) or increased levels (basket cells). GABA receptor density, number and protein expression are all decreased in the cerebellum and in select cortical areas. GABAA and GABAB subunit protein expression was significantly reduced in cerebellum, BA 9 and BA 40. Benzodiazepine binding sites were significantly reduced in the hippocampus and anterior cingulate cortex (BA 24). Taken together, data from these studies suggest that there is a marked dysregulation of the inhibitory GABA system in the autism brain affecting particular biomarkers localized to specific cell types and lamina likely influencing circuitry and behavior.
登录
查看更多内容
影响因子：
14.5
作者：
Bailey, A;Luthert, P;Lantos, P
通讯作者：
Lantos, P
影响因子：
2.7
作者：
DeLorey, Timothy M.;Sahbaie, Peyman;Clark, J. David
通讯作者：
Clark, J. David
影响因子：
2.5
作者：
ESCLAPEZ, M;TILLAKARATNE, NJK;HOUSER, CR
通讯作者：
HOUSER, CR
影响因子：
3.5
作者：
Fatemi, S. Hossein;Folsom, Timothy D.;Reutiman, Teri J.;Thuras, Paul D.
通讯作者：
Thuras, Paul D.
影响因子：
6.1
作者：
Han, Ying;Qin, Jiong;Yang, Zhi-Xian
通讯作者：
Yang, Zhi-Xian