Neuroglial activation and neuroinflammation in the brain of patients with autism
Neuroglial activation and neuroinflammation in the brain of patients with autism
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DOI：
10.1002/ana.20315
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发表时间：
2005-01-01
影响因子：
11.2
通讯作者：
Pardo, CA
中科院分区：
文献类型：
--
作者：
Vargas, DL;Nascimbene, C;Pardo, CA
自闭症是一种神经发育障碍，其特征是交流和社会互动受损，并可能伴有智力迟钝和癫痫。尽管有证据表明遗传、环境和免疫因素可能在其发病机制中起作用，但其原因仍不清楚。为了研究免疫介导的机制是否参与了自闭症的发病机制，我们使用免疫细胞化学，细胞因子蛋白阵列和酶联免疫吸附试验来研究自闭症患者的脑组织和脑脊液（CSF），并确定神经胶质细胞和炎症反应的程度及其细胞因子表达谱。从小脑，额中，扣带回和脑组织，从11例自闭症患者尸检获得用于形态学研究。新鲜冷冻组织可从七个病人和CSF从六个生活自闭症患者用于细胞因子蛋白质谱。我们证明了一个活跃的神经炎症过程中的大脑皮层，白色物质，特别是在小脑的自闭症患者。免疫细胞化学研究表明，小胶质细胞和星形胶质细胞的显着活化，细胞因子分析表明，巨噬细胞趋化蛋白（MCP）-1和肿瘤生长因子β 1，来自神经胶质细胞，是最普遍的细胞因子在脑组织中。CSF显示出独特的细胞因子促炎特征，包括MCP-1的显著增加。我们的研究结果表明，先天性神经免疫反应在一个不确定的比例的自闭症患者中起着致病作用，这表明未来的治疗可能涉及改变大脑中的神经胶质反应。
Autism is a neurodevelopmental disorder characterized by impaired communication and social interaction and may be accompanied by mental retardation and epilepsy. Its cause remains unknown, despite evidence that genetic, environmental, and immunological factors may play a role in its pathogenesis. To investigate whether immune-mediated mechanisms are involved in the pathogenesis of autism, we used immunocytochemistry, cytokine protein arrays, and enzyme-linked immunosorbent assays to study brain tissues and cerebrospinal fluid (CSF) from autistic patients and determined the magnitude of neuroglial and inflammatory reactions and their cytokine expression profiles. Brain tissues from cerebellum, midfrontal, and cingulate gyrus; obtained at autopsy from 11 patients with autism were used for morphological studies. Fresh-frozen tissues available from seven patients and CSF from six living autistic patients were used for cytokine protein profiling. We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably in cerebellum of autistic patients. Immunocytochemical studies showed marked activation of microglia and astroglia, and cytokine profiling indicated that macrophage chemoattractant protein (MCP)-1 and tumor growth factor-beta1, derived from neuroglia, were the most prevalent cytokines in brain tissues. CSF showed a unique proinflammatory profile of cytokines, including a marked increase in MCP-1. Our findings indicate that innate neuroimmune reactions play, a pathogenic role in an undefined proportion of autistic patients, suggesting that future therapies might involve modifying neuroglial responses in the brain.