THE NEUROANATOMICAL BASIS OF SOCIAL-AFFECTIVE DEFICITS IN AUTISM

自闭症社交情感缺陷的神经解剖学基础

• 批准号: 7560756
• 负责人: GENE J BLATT
• 金额: $ 17.63万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7560756
• 关键词: GABA aminotransferase; GABA receptor; amygdala; autism; autoradiography; behavioral /social science research tag; cellular pathology; cingulate gyrus; communication behavior; cooperative study; frontal lobe /cortex; hippocampus; human tissue; immunocytochemistry; interneurons; ligands; limbic system; membrane transport proteins; mental disorders; microglia; neuropathology; postmortem; psychopathology; receptor binding; serotonin; social behavior

Neuropathological findings in autism have consistently implicated the hippocampus and amygdala, two key limbic system structures with specific but wide-ranging connections throughout many cortical regions. While the hippocampus has important functions in declarative and short term memory processes, the amygdala in contrast has been implicated in emotions, fear, anxiety and is critically important for social interaction with 3eers and the environment, in autism, individuals have difficulties with declarative memory and with socioemotional and affective behavior. Although the hippocampus and amygdala are the subject of many ongoing research studies, the direct and indirect cortical connectivity of these two key brain areas have not been well studied in autism. Thus, the present study will investigate six key cortical areas including two in the frontal lobe (medial and orbital frontal cortex), three areas in the cingulate gyrus (anterior and posterior cingulate and retrosplenial cortex) and the temporal lobe fusiform face area in the fusiform gyrus, each of which have important connections with either the hippocarnpus, amygdala or both. The hypothesis is that the circuitry within these limbic cortices is altered contributing to the social affective behavioral deficits in autism. The cellular structure and cortical cytoarchitecture will be studied via standard Nissl stains for cellular pathology in the six cortices. Since it now appears that abnormalities in benzodiazepine binding sites and GABA-A receptors have been identified in the hippocampus, the GABAergic will be investigated in the six cortical areas using a variety of methods. Immunocytochemistry will quantify subpopulations of cortical GABAergic intemeurons and assess the functional activity utilizing antibodies dierected against three types of GABAergic transporters (uptake sites). In addition, in vitro multiple concentration ligand binding will quantify the density of binding and affinity to bind benzodiazepine and GABA-A sites as well as three types of serotonergic receptors, another transmitter system implicated in autistic spectrum. Finally, the dynamic state within the brain of autistic individuals will be assessed utilizing antibodies toward two types of neuroglia: microglia and astrocytes. Microglial aggregations at sites of neuropathological changes wilt be a focus of the study with the hypothesis that autism is an ongoing process and not a static disorder.

自闭症中的神经病理学发现始终牵涉到海马和杏仁核，这是两个关键的边缘系统结构，这些结构在许多皮质区域具有特定但广泛的连接。尽管海马在声明性和短期记忆过程中具有重要功能，但相比之下，杏仁核与情感，恐惧，焦虑症有关，对于与3Eers和环境的社交互动至关重要 和情感行为。尽管海马和杏仁核是许多人的主题 正在进行的研究研究，这两个关键大脑区域的直接和间接皮质连通性在自闭症中尚未得到很好的研究。因此，本研究将研究六个关键的皮质区域，包括额叶中的两个（内侧和轨道额叶皮质），扣带回的三个区域（前扣带回和后扣带回和垂直皮层）和颞叶梭形面部面向梭形的圆锥形圆锥形区域，它们都具有重要的连接，均与amipsan a ammyn amhyg。假设是，这些边缘皮层内的电路正在改变自闭症的社会情感行为缺陷。细胞结构和皮质细胞结构将通过标准NISSL染色来研究六个皮质中的细胞病理学。因为现在看来苯并二氮卓的异常结合 在海马中已经鉴定出了位点和GABA-A受体，将使用多种方法在六个皮质区域研究GABA能。免疫细胞化学将量化皮质GABA能元素的亚群，并评估使用针对三种类型的GABA能转运蛋白（摄取位点）差异的抗体的功能活性。另外，体外多浓度配体结合将量化结合苯二氮卓和GABA-A位点的结合和亲和力的密度，以及三种类型的血清素能受体，这是另一种涉及自闭症谱的发射机系统。最后，动态 使用对两种类型的神经胶质的抗体：小胶质细胞和星形胶质细胞的抗体，将评估自闭症个体内部的状态。神经病理学变化部位的小胶质聚集是研究的重点，假设自闭症是一种持续的过程而不是静态疾病。