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首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders
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Dysregulated brain immunity and neurotrophin signaling in Rett syndrome and autism spectrum disorders

机译：Rett综合征和自闭症谱系障碍的大脑免疫和神经营养因子信号调节异常

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Rett syndrome is a neurodevelopmental disorder, which occurs in about 1:15,000 females and presents with neurologic and communication defects. It is transmitted as an X-linked dominant linked to mutations of the methyl-CpG-binding protein (MeCP2), a gene transcription suppressor, but its definitive pathogenesis is unknown thus hindering development of effective treatments. Almost half of children with Rett syndrome also have behavioral symptoms consistent with those of autism spectrum disorders (ASDs). PubMed was searched (2005-2014) using the terms: allergy, atopy, brain, brain-derived neurotrophic factor (BDNF), corticotropin-releasing hormone (CRH), cytokines, gene mutations, inflammation, mast cells (MCs), microglia, mitochondria, neurotensin (NT), neurotrophins, seizures, stress, and treatment. There are a number of intriguing differences and similarities between Rett syndrome and ASDs. Rett syndrome occurs in females, while ASDs more often in males, and the former has neurologic disabilities unlike ASDs. There is evidence of dysregulated immune system early in life in both conditions. Lack of microglial phagocytosis and decreased levels of BDNF appear to distinguish Rett syndrome from ASDs, in which there is instead microglia activation and/or proliferation and possibly defective BDNF signaling. Moreover, brain mast cell (MC) activation and focal inflammation may be more prominent in ASDs than Rett syndrome. The flavonoid luteolin blocks microglia and MC activation, provides BDNF-like activity, reverses Rett phenotype in mouse models, and has a significant benefit in children with ASDs. Appropriate formulations of luteolin or other natural molecules may be useful in the treatment of Rett syndrome. (C) 2014 Elsevier B.V. All rights reserved.
机译：Rett综合征是一种神经发育障碍，约1：15,000的女性发生，并伴有神经系统和沟通缺陷。它以X连锁显性基因的形式传播，并与基因转录抑制物甲基CpG结合蛋白（MeCP2）的突变相关，但尚不清楚其确切的发病机理，因此阻碍了有效治疗方法的发展。几乎一半的Rett综合征儿童也有与自闭症谱系障碍（ASD）一致的行为症状。 （2005-2014）使用以下术语对PubMed进行了搜索：变态反应，特应性，大脑，脑源性神经营养因子（BDNF），促肾上腺皮质激素释放激素（CRH），细胞因子，基因突变，炎症，肥大细胞（MCs），小胶质细胞，线粒体，神经降压素（NT），神经营养蛋白，癫痫发作，压力和治疗。 Rett综合征和ASD之间存在许多有趣的区别和相似之处。 Rett综合征在女性中发生，而ASD在男性中更为常见，而前者具有与ASD不同的神经功能障碍。有证据表明，在这两种情况下，生命早期免疫系统失调。缺乏小胶质细胞吞噬作用和降低的BDNF水平似乎使Rett综合征与ASD区别开来，在ASD中，小胶质细胞激活和/或增殖以及可能的BDNF信号传导缺陷。而且，在ASD中，脑肥大细胞（MC）的激活和局灶性炎症可能比Rett综合征更为突出。黄酮类木犀草素阻断小胶质细胞和MC激活，提供类似BDNF的活性，在小鼠模型中逆转Rett表型，对患有ASD的儿童具有显着的益处。木犀草素或其他天然分子的适当制剂可用于治疗雷特综合征。 （C）2014 Elsevier B.V.保留所有权利。

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