期刊
ACTA NEUROPATHOLOGICA COMMUNICATIONS
卷 1, 期 -, 页码 -出版社
BMC
DOI: 10.1186/2051-5960-1-61
关键词
7 Idiopathic autism; Chromosome-15q11.2-q13 duplication; Amyloid-beta peptide; Oxidative stress; Malondialdehyde; 4-hydroxy-2-nonenal
资金
- NYS Office
- Department of Defense Autism Spectrum Disorders Research Program [AS073234]
- Autism Speaks
Background: Autism is a neurodevelopmental disorder of unknown etiopathogenesis associated with structural and functional abnormalities of neurons and increased formation of reactive oxygen species. Our previous study revealed enhanced accumulation of amino-terminally truncated amyloid-beta (A beta)in brain neurons and glia in children and adults with autism. Verification of the hypothesis that intraneuronal A beta may cause oxidative stress was the aim of this study. Results: The relationships between neuronal A beta and oxidative stress markers-4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA)-were examined in the frontal cortex from individuals aged 7-32 years with idiopathic autism or with chromosome 15q11.2-q13 duplications (dup(15)) with autism, and age-matched controls. Quantification of confocal microscopy images revealed significantly higher levels of neuronal N-truncated A beta and HNE and MDA in idiopathic autism and dup(15)/autism than in controls. Lipid peroxidation products were detected in all mitochondria and lipofuscin deposits, in numerous autophagic vacuoles and lysosomes, and in less than 5% of synapses. Neuronal A beta was co-localized with HNE and MDA, and increased A beta levels correlated with higher levels of HNE and MDA. Conclusions: The results suggest a self-enhancing pathological process in autism that is initiated by intraneuronal deposition of N-truncated A beta in childhood. The cascade of events includes altered APP metabolism and abnormal intracellular accumulation of N-terminally truncated A beta which is a source of reactive oxygen species, which in turn increase the formation of lipid peroxidation products. The latter enhance A beta deposition and sustain the cascade of changes contributing to metabolic and functional impairments of neurons in autism of an unknown etiology and caused by chromosome 15q11.2 q13 duplication.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据