Measuring Altered Glutathione in Children with Autism Spectrum Disorder

测量自闭症谱系障碍儿童的改变谷胱甘肽

基本信息

批准号：
10055287
负责人：
Richard Anthony Edward Edden
金额：
$ 25.97万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-24 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10055287
关键词：
Affect Antioxidants Apoptosis Brain Brain region Child Cognition Cognitive Cognitive deficits DNA Repair Data Development Disease Early Intervention Environmental Risk Factor Family Free Radicals Functional disorder Future Genetic Glutathione Glutathione Disulfide Goals Grant Health Healthcare Systems Heterogeneity Human Impaired cognition Impairment Individual Individual Differences Lead Life Magnetic Resonance Spectroscopy Maintenance Measurement Measures Medial Metabolic Methods Mind Motor Neurologic Deficit Neurologic Examination Neurons Neurotransmitters Nitric Oxide Oxidation-Reduction Oxidative Stress Oxides Peripheral Physical Examination Plasma Play Prefrontal Cortex Process Reactive Oxygen Species Regulation Resolution Role Severities Signal Transduction Techniques Testing Work autism diagnostic observation schedule autism spectrum disorder autistic children behavior measurement behavioral outcome cell injury cohort developmental disease dimer experimental study functional disability gamma-Aminobutyric Acid in vivo innovation neuropathology neurophysiology neurotransmission novel peripheral blood prevent repetitive behavior social theories

项目摘要

Project summary Autism Spectrum Disorder (ASD) is characterized by impairments in social and communicative function and repetitive behaviors. Recent work suggests that oxidative stress (arising from both genetic and environmental causes) is a contributing factor to the neuropathology of ASD. Emerging evidence suggests that increased oxidative stress may contribute to the neuronal and cognitive impairments seen in children with Autism Spectrum Disorder (ASD). Glutathione (GSH) is the main redox compound in the brain, and reduced GSH during development may lead to such increases in oxidative stress and may be a primary cause of secondary neurophysiological impairments in ASD. GSH can be measured using edited Magnetic Resonance Spectroscopy (MRS). Here, we propose using a highly novel MRS technique (HERMES) to measure GSH in the brain of children with ASD and investigate its relation to functional behavioral measures of autism, and peripheral markers of oxidative stress, work not previously performed. The novelty lies in the application in children, using a recently developed, more specific and valid MRS technique. Increased oxidative stress, and associated GSH dysfunction, may therefore be an important contributor to autism-associated alterations in brain development, contributing in turn to cognitive and social impairments common in ASD. Understanding the role of oxidative stress in ASD is important for understanding the emergence of ASD and offers a promising target for future early interventions to increase GSH concentration in the brain.

项目概要自闭症谱系障碍 (ASD) 的特点是社交和沟通功能障碍重复的行为。最近的研究表明，氧化应激（由遗传和环境引起）原因）是 ASD 神经病理学的一个促成因素。新出现的证据表明，增加氧化应激可能导致自闭症儿童的神经元和认知障碍频谱障碍（ASD）。谷胱甘肽 (GSH) 是大脑中主要的氧化还原化合物，还原性 GSH 在发育过程中可能会导致氧化应激的增加，并且可能是继发性应激的主要原因自闭症谱系障碍 (ASD) 中的神经生理学损伤。可以使用编辑后的磁共振来测量 GSH 光谱学（MRS）。在这里，我们建议使用一种高度新颖的 MRS 技术 (HERMES) 来测量 GSH 自闭症儿童的大脑并研究其与自闭症功能行为测量的关系，以及氧化应激的外周标志物，以前未进行过的工作。新颖之处在于应用儿童，使用最近开发的、更具体和有效的 MRS 技术。氧化应激增加，以及因此，与自闭症相关的 GSH 功能障碍可能是导致自闭症相关改变的一个重要因素。大脑发育，进而导致自闭症谱系障碍中常见的认知和社交障碍。理解氧化应激在自闭症谱系障碍中的作用对于理解自闭症谱系障碍的出现很重要，并提供了未来早期干预措施增加大脑中谷胱甘肽浓度的有希望的目标。