Defining interneuron deficits in Down syndrome brain.

 描述(申请人提供)：唐氏综合症(DS)是导致智力残疾的最常见的遗传原因，但导致DS患者特定认知缺陷的神经解剖异常尚未得到很好的定义。组织病理学观察，虽然有限，但始终暗示神经元数量减少是DS大脑皮层的主要缺陷。然而，受影响的神经元亚型的身份尚不清楚，这种信息的缺乏既减少了我们对DS神经病理学的知识，也减少了我们定义潜在治疗方法的能力。因此，定义DS中减少的神经元对于我们理解DS智能障碍的神经生物学基础是至关重要的 大脑皮层。这一自成一体的小提议旨在检验这样一个简单的假设，即人类DS皮层中的中间神经元较少。将在死后DS人脑中识别和计数抑制性中间神经元，并使用现代免疫染色和定量技术与对照组进行比较。

 DESCRIPTION (provided by applicant): Down syndrome (DS) is the most common genetic cause of intellectual disability but the neuroanatomical abnormalities that contribute to specific cognitive deficits in individuals with DS have not been well defined. Histopathological observations, though limited, have consistently implicated reduced neuron number as a major defect in the DS cerebral cortex. Yet the identity of the neuron subtype that is affected is not known and this lack of information lessens both our knowledge of DS neuropathology and our ability to define potential therapies. It is therefore critical to our understanding of the neurobiological basis of intellectual disability in DS to define the neurons that are reduced in DS cerebral cortex. This small self-contained proposal aims to test the simple hypothesis that there are fewer interneurons in human DS cortex. Inhibitory interneurons will be identified and counted in post-mortem DS human brain and compared to controls using modern techniques for immunostaining and quantification.