Defining interneuron deficits in Down syndrome brain.

定义唐氏综合症大脑的中间神经元缺陷。

• 批准号: 9034147
• 负责人: ANITA BHATTACHARYYA
• 金额: $ 8.01万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9034147
• 关键词: Address; Adult; Affect; Alzheimer' s Disease; Area; Biological; Brain; Brain region; Cerebral cortex; Cognitive deficits; Data; Defect; Development; Down Syndrome; Electrophysiology (science); Foundations; Future; Generations; Genetic; Gestational Age; Histopathology; Human; Immunohistochemistry; In Vitro; Individual; Intellectual functioning disability; Interneurons; Knowledge; Lead; Life; Morphology; Mus; Nerve Degeneration; Neurobiology; Neurons; Parvalbumins; Pathology; Population; Property; Public Health; Research; Somatostatin; Techniques; Testing; Therapeutic; Time; Tissues; Translating; Work; base; brain tissue; calbindin; calretinin; human data; human fetus tissue; in vivo; induced pluripotent stem cell; insight; migration; mouse model; neurogenesis; neuropathology; protein expression; public health relevance; young adult

 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.

 描述（由申请人提供）：唐氏综合征（DS）是智力残疾的最常见遗传原因，但导致DS患者特定认知缺陷的神经解剖学异常尚未得到很好的定义。组织学观察，虽然有限，一直牵连神经元数量减少的DS大脑皮层的主要缺陷。然而，受影响的神经元亚型的身份是未知的，这种信息的缺乏减少了我们对DS神经病理学的知识和我们定义潜在疗法的能力。因此，确定DS中减少的神经元对我们理解DS中智力残疾的神经生物学基础至关重要 大脑皮层这个小的独立的提议旨在测试一个简单的假设，即人类DS皮层中的中间神经元较少。将在死后DS人脑中鉴定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进行比较。