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Microglial and neuronal abnormalities in the autistic brain .

机译：自闭症脑的小胶质细胞和神经元异常。

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摘要

Autism is a neurodevelopmental disorder of social cognition that is marked by frontally pronounced early brain overgrowth. Functional magnetic resonance imaging studies have shown that the regions of the brain that display the greatest overgrowth early in life, such as dorsolateral prefrontal cortex, also demonstrate significant deficits in older children and adults with the disorder. However, there is relatively little information about the cellular abnormalities that underlie these observed macrostructural and functional alterations. A single study has directly observed altered glial morphology in the postmortem autistic frontal cortex, while a handful of studies have observed neuron loss in older subjects with autism.;Therefore, we conducted a series of experiments aimed at elucidating both population and organizational abnormalities in the microglial and neuronal populations in the autistic dorsolateral prefrontal cortex. In chapter II of this thesis, we use optical disector and isotropic nucleator to describe Iba-1 positive microglial density and volume in an unprecedentedly large sample of postmortem autism tissue. Our findings indicate that increased density and somal volume are present in a sizeable fraction of subjects with autism from an early age, including during the period of early brain overgrowth, and that these alterations are not attributable to seizure. In chapter III, we turn to an examination of average horizontal neuron distance in the same set of subjects. We describe an increase in horizontal neuronal spacing early in life that likely reflects an early overproduction of neuropil, while confirming previous findings of reduced horizontal distance in adults, suggesting a gradual degenerative decline. In chapter IV, we turn to spatial pattern analysis to examine whether there are alterations in neuronal and microglial organization. We discover emergent alterations in local neuron-neuron and microglia-microglia organization across the autistic lifespan, along with group differences in local microglia-neuron clustering that do not show a developmental trend.;These experiments describe several novel microstructural features of the developing autistic brain, and suggest that microglial activation and neuropil overproduction are present during early brain overgrowth and are followed by gradual neuropil degeneration and loss of cellular organization in adolescents and adults that may be related at least in part to ongoing microglial activation. Further investigation of cellular and microstructural abnormalities in the autistic brain may hold the key to understanding the complex set of alterations that underlie this disorder, and point the way towards diagnostic strategies and therapeutic instruments.
机译：自闭症是一种社会认知的神经发育障碍，其特征是前脑明显过度生长。功能磁共振成像研究表明，在生命早期表现出最大的过度生长的大脑区域，例如背外侧前额叶皮层，也显示出患有这种疾病的较大儿童和成年人的明显缺陷。但是，关于这些观察到的宏观结构和功能改变基础的细胞异常的信息相对较少。一项研究直接观察了死后自闭症额叶皮层的胶质细胞形态改变，而少数研究则观察到自闭症老年患者的神经元丢失。因此，我们进行了一系列实验，旨在阐明自闭症患者额叶和组织异常。自闭性背外侧前额叶皮层中的小胶质细胞和神经元种群。在本文的第二章中，我们使用光学解剖器​​和各向同性成核剂来描述死后自闭症组织前所未有的大样本中Iba-1阳性小胶质细胞的密度和体积。我们的研究结果表明，自幼就包括自闭症早期在内的相当一部分自闭症患者中存在相当大的密度和体体积，并且这些改变并非归因于癫痫发作。在第三章中，我们转向检查同一组受试者的平均水平神经元距离。我们描述了生命早期水平神经元间距的增加，这可能反映了神经绒毛的早期过度生产，同时证实了成年人水平距离减小的先前发现，提示逐渐退化。在第四章中，我们转向空间模式分析，以检查神经元和小胶质细胞组织是否发生改变。我们发现自闭症寿命期间局部神经元-神经元和小胶质细胞-小胶质细胞组织出现了新的变化，以及局部小胶质细胞-神经元聚类的群体差异并未显示出发展趋势。 ，并提示在早期大脑过度生长期间存在小胶质细胞激活和神经胶质过度生成，随后在青少年和成年人中逐渐发生神经胶质退化和细胞组织丧失，这可能至少部分与正在进行的小胶质细胞活化有关。对自闭症大脑中的细胞和微结构异常的进一步研究可能是理解这一疾病背后复杂变化的关键，并为诊断策略和治疗手段指明了方向。

著录项

  • 作者

    Morgan, John T.;

  • 作者单位

    University of California, San Diego.;

  • 授予单位 University of California, San Diego.;
  • 学科 Biology Neuroscience.;Biology Cell.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 174 p.
  • 总页数 174
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

  • 入库时间 2022-08-17 11:38:19

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