PRIMATE MODELS OF AUTISM

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 自闭症是一种神经发育障碍，其特征是社交行为和沟通障碍，并存在重复或刻板印象的行为。自闭症的病因目前尚不清楚。然而，有证据表明，针对胎儿脑组织的母体自身抗体可能是导致部分自闭症病例的原因。为了支持这一点，我们最近在患有自闭症的多个孩子的母亲中发现了一种针对人类胎儿脑组织(以及针对恒河猴脑组织)的自身抗体产生的特征模式。我们的初步研究表明，与对照猴子相比，产前暴露于这些母亲的Ig G类抗体的恒河猴会产生更多的全身运动刻板印象(自闭症的一个定义症状)。虽然这些初步发现令人震惊，但它们是基于少数接受治疗的受试者、接触纯化的免疫球蛋白的有限窗口以及相对有限的行为观察期。延长免疫球蛋白暴露的时间可能会导致其他行为异常，更能指示完全自闭症综合征。我们建议通过增加实验受试者的数量和将一部分实验受试者的免疫球蛋白暴露时间延长到第二个三个月，来复制和扩展我们对自闭症这一有希望的免疫学模型的研究。我们将加强和扩大治疗动物的行为观察，并进行结构神经成像研究。我们建议首先在发育的头两年对受试者进行广泛的行为评估。我们将定量分析物种典型行为在各种社会背景下的出现，以及旨在探索依恋、社会优势、社会动机和恐惧反应的实验。这些研究还将评估交易互动的质量，并检测诸如刻板印象等异常行为。我们还将进行详细的纵向磁共振成像(MRI)研究，以评估大脑发育时间进程的差异。我们将把MRI分析的重点放在自闭症神经病理中最常见的大脑区域，包括额叶、杏仁核和小脑，以及与刻板印象相关的结构，如基底节。这项工作代表了一种很有前途的自闭症动物模型，并可能对这种疾病的诊断、预防和治疗产生直接影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Autism is a neurodevelopmental disorder characterized by deficits in social behavior and communication and the presence of repetitive or stereotyped behaviors. The etiology(ies) of autism are currently unknown. However, evidence suggests that maternal autoantibodies directed against fetal brain tissue are a putative cause for a subset of autism cases. In support of this, we have recently identified a characteristic pattern of autoantibody production to human fetal brain tissue (and to rhesus monkey brain tissue) in 20% of mothers of multiple children with autism. Our preliminary studies indicate that rhesus monkeys, prenatally exposed to IgG class antibodies from these mothers, produce more whole body motor stereotypies (a defining symptom of autism) compared to control monkeys. These preliminary findings, while striking, are based on a small number of treated subjects, a restricted window of exposure to the purified IgG and a relatively limited period of behavioral observations. It is possible that extending the duration of IgG exposure may result in other behavioral abnormalities more indicative of the complete autistic syndrome. We propose to replicate and extend our research on this promising immunological model of autism by increasing the number of experimental subjects and increasing the duration of IgG exposure into the second trimester for a subset of the experimental subjects. We will enhance and extend the behavioral observations of the treated animals and carry out a structural neuroimaging study. We propose first to conduct an extensive behavioral assessment of the subjects during the first two years of development. We will quantitatively analyze the emergence of species typical behaviors in a variety of social contexts and in experiments designed to probe attachments, social dominance, social motivations, and fear reactions. These studies will also evaluate the quality of transactional interactions and detect abnormal behaviors such as stereotypies. We will also carry out a detailed longitudinal magnetic resonance imaging (MRI) study to evaluate differences in the time course of brain development. We will focus the MRI analyses on brain regions most commonly implicated in the neuropathology of autism, including the frontal lobes, amygdala and cerebellum and on structures associated with stereotypies such as the basal ganglia. This work represents a promising animal model of autism and may have direct implications for diagnosis, prevention and treatment of this disorder.