Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.
Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders.
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DOI：
10.1186/s13229-016-0110-z
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发表时间：
2016
期刊：
影响因子：
6.2
通讯作者：
Fasano A
中科院分区：
文献类型：
--
作者：
Fiorentino M;Sapone A;Senger S;Camhi SS;Kadzielski SM;Buie TM;Kelly DL;Cascella N;Fasano A
自闭症谱系障碍(ASD)是一种复杂的疾病，其发病机制可能归因于基因与环境的相互作用。目前还没有明确的机制来解释环境因素是如何导致ASD的，尽管已经提出了炎症和免疫的参与。通过受损的肠道屏障的不适当的抗原运输，然后这些抗原或免疫激活的复合体通过允许的血脑屏障(BBB)，可能是导致这些疾病的连锁反应的一部分。我们的目标是调查血脑屏障和肠道通透性改变是否是ASD病理生理学的一部分。分析了ASD、精神分裂症(SCZ)和健康人(HC)的大脑皮层和小脑组织以及ASD和HC的十二指肠活检组织的基因和蛋白质表达谱。对紧密连接和其他与神经血管单位完整性和功能相关的关键分子以及神经炎症进行了研究。在ASD皮质和小脑中，claudin(CLDN)-5和-12表达增加。CDN-3、三细胞蛋白和基质金属蛋白酶-9在ASD皮质区较高。IL-8、tPA、IBA-1在SCZ皮质表达下调，IL-1b在SCZ小脑表达升高。在两个大脑区域分析的大多数基因上，SCZ和ASD都有差异。ASD皮质和小脑中CLDN-5蛋白表达增加，而ASD和SCZ皮质中CLDN-12蛋白表达均减少。在肠道中，75%的ASD样本与对照组相比，屏障形成TJ组分(CLDN-1、OCLN、TIC)的表达减少，而形成孔洞的CLDN(CLDN-2、-10、-15)的表达增加。在ASD的大脑中，与血脑屏障完整性相关的基因表达发生了变化，伴随着神经炎症的增加，可能还损害了肠道屏障的完整性。虽然这些发现似乎是ASD特有的，但更多不同的SCZ亚组的可能性应该通过更多的研究来探索。
Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene–environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood–brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. Claudin (CLDN)-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3, tricellulin, and MMP-9 were higher in the ASD cortex. IL-8, tPA, and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components (CLDN-1, OCLN, TRIC), whereas 66% had increased pore-forming CLDNs (CLDN-2, -10, -15) compared to controls. In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies.
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影响因子：
2.4
作者：
Coelho, Fernanda Matos;Reis, Helton Jose;Teixeira, Antonio Lucio
通讯作者：
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影响因子：
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DOI：
10.1097/mpg.0b013e3181dcc4a5
发表时间：
2010-10-01
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作者：
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