PRIMATE MODELS OF AUTISM

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 孤独症是一种神经发育障碍，其特征是社会行为和沟通的缺陷以及重复或刻板行为的存在。 自闭症的病因目前还不清楚。 然而，有证据表明，针对胎儿脑组织的母体自身抗体是自闭症病例子集的假定原因。 为了支持这一点，我们最近在20%的多个自闭症儿童的母亲中发现了人类胎儿脑组织（和恒河猴脑组织）自身抗体产生的特征模式。 我们的初步研究表明，恒河猴，产前暴露于IgG类抗体从这些母亲，产生更多的全身运动刻板印象（自闭症的定义症状）相比，控制猴子。 这些初步发现虽然引人注目，但基于少量治疗受试者、暴露于纯化IgG的有限窗口和相对有限的行为观察期。 这是可能的，延长IgG暴露的持续时间可能会导致其他行为异常，更表明完全自闭症综合征。 我们建议通过增加实验对象的数量和增加实验对象子集的IgG暴露到妊娠中期的持续时间来复制和扩展我们对这种有前途的自闭症免疫模型的研究。 我们将加强和扩大对治疗动物的行为观察，并进行结构神经成像研究。 我们建议首先在头两年的发展过程中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，并在实验中设计探测附件，社会优势，社会动机和恐惧反应。 这些研究还将评估交易互动的质量，并发现异常行为，如刻板印象。 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分析的重点放在最常涉及自闭症神经病理学的大脑区域，包括额叶、杏仁核和小脑，以及与刻板印象相关的结构，如基底神经节。 这项工作代表了一个有前途的自闭症动物模型，可能对这种疾病的诊断，预防和治疗有直接的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.