PRIMATE MODELS OF AUTISM

自闭症灵长类动物模型

• 批准号: 8172571
• 负责人: Melissa Dawn Bauman
• 金额: $ 11.41万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172571
• 关键词: Amygdaloid structure; Animal Model; Animals; Antibodies; Autistic Disorder; Autoantibodies; Basal Ganglia; Behavior; Behavior assessment; Behavioral; Brain; Brain region; Cerebellum; Characteristics; Child; Communication; Computer Retrieval of Information on Scientific Projects Database; Development; Diagnosis; Disease; Employee Strikes; Etiology; Exposure to; Fright; Funding; Grant; Human; Image Analysis; Immunoglobulin G; Immunological Models; Institution; Macaca mulatta; Magnetic Resonance Imaging; Modeling; Monkeys; Mothers; Motivation; Motor; Neurodevelopmental Disorder; Pattern; Prevention; Primates; Production; Reaction; Research; Research Personnel; Resources; Second Pregnancy Trimester; Social Behavior; Social Dominance; Social Environment; Source; Stereotyped Behavior; Structure; Symptoms; Syndrome; Time; United States National Institutes of Health; Work; base; behavior observation; brain tissue; design; fetal; frontal lobe; neuroimaging; neuropathology; prenatal exposure; research study; social; species typical behavior

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 自闭症是一种神经发育障碍，其特征是社会行为和沟通不足以及重复或刻板印象的存在。 自闭症的病因（IES）目前未知。 但是，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的一部分的推定原因。 为了支持这一点，我们最近在20％的自闭症儿童的母亲中确定了人类胎儿脑组织（以及恒河猴脑组织）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，与这些母亲的IgG类抗体暴露于IgG类抗体（自闭症的定义症状）。 这些初步发现虽然引人注目，但基于少数治疗的受试者，受到纯化IgG的限制窗口以及相对有限的行为观察期。 延长IgG暴露持续时间可能会导致其他行为异常更多地表明完整的自闭症综合征。 我们建议通过增加实验受试者的数量并将IgG暴露的持续时间增加到第二个孕期，以复制和扩展对这种有希望的自闭症免疫学模型的研究。 我们将增强和扩展治疗动物的行为观察，并进行一项结构性神经影像学研究。 我们首先建议在开发的头两年中对受试者进行广泛的行为评估。 我们将定量分析物种在各种社会背景下的典型行为的出现以及旨在探究依恋，社会优势，社会动机和恐惧反应的实验中的出现。 这些研究还将评估交易相互作用的质量并检测异常行为，例如刻板印象。 我们还将进行一项详细的纵向磁共振成像（MRI）研究，以评估大脑发育时间过程的差异。 我们将把MRI分析重点放在与自闭症神经病理学有关的大脑区域上，包括额叶叶，杏仁核和小脑以及与基础神经节等刻板印象相关的结构。 这项工作代表了一种有希望的自闭症动物模型，可能对诊断，预防和治疗这种疾病具有直接影响。