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Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders / M. FIORENTINO in Molecular Autism, 7 (2016)
[article]
Titre : Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : M. FIORENTINO, Auteur ; A. SAPONE, Auteur ; S. SENGER, Auteur ; S. S. CAMHI, Auteur ; S. M. KADZIELSKI, Auteur ; Timothy M. BUIE, Auteur ; D. L. KELLY, Auteur ; N. CASCELLA, Auteur ; A. FASANO, Auteur Article en page(s) : 49p. Langues : Anglais (eng) Mots-clés : Adolescent Adult Autism Spectrum Disorder/genetics/immunology/metabolism/pathology Biopsy Blood-Brain Barrier/immunology/metabolism/pathology Case-Control Studies Cerebellum/immunology/metabolism/pathology Cerebral Cortex/immunology/metabolism/pathology Child Child, Preschool Claudin-3/genetics/immunology Claudin-5/genetics/immunology Claudins/genetics/immunology DNA-Binding Proteins/genetics/immunology Duodenum/immunology/metabolism/pathology Female Gene Expression Humans Interleukin-1beta/genetics/immunology Interleukin-8/genetics/immunology MARVEL Domain Containing 2 Protein/genetics/immunology Male Matrix Metalloproteinase 9/genetics/immunology Middle Aged Permeability Schizophrenia/genetics/immunology/metabolism/pathology Tight Junctions/immunology/metabolism/pathology Autism spectrum disorders Blood-brain barrier Duodenal biopsies Gut permeability Gut-brain axis Neuroinflammation Postmortem brain Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. En ligne : http://dx.doi.org/10.1186/s13229-016-0110-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328
in Molecular Autism > 7 (2016) . - 49p.[article] Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders [Texte imprimé et/ou numérique] / M. FIORENTINO, Auteur ; A. SAPONE, Auteur ; S. SENGER, Auteur ; S. S. CAMHI, Auteur ; S. M. KADZIELSKI, Auteur ; Timothy M. BUIE, Auteur ; D. L. KELLY, Auteur ; N. CASCELLA, Auteur ; A. FASANO, Auteur . - 49p.
Langues : Anglais (eng)
in Molecular Autism > 7 (2016) . - 49p.
Mots-clés : Adolescent Adult Autism Spectrum Disorder/genetics/immunology/metabolism/pathology Biopsy Blood-Brain Barrier/immunology/metabolism/pathology Case-Control Studies Cerebellum/immunology/metabolism/pathology Cerebral Cortex/immunology/metabolism/pathology Child Child, Preschool Claudin-3/genetics/immunology Claudin-5/genetics/immunology Claudins/genetics/immunology DNA-Binding Proteins/genetics/immunology Duodenum/immunology/metabolism/pathology Female Gene Expression Humans Interleukin-1beta/genetics/immunology Interleukin-8/genetics/immunology MARVEL Domain Containing 2 Protein/genetics/immunology Male Matrix Metalloproteinase 9/genetics/immunology Middle Aged Permeability Schizophrenia/genetics/immunology/metabolism/pathology Tight Junctions/immunology/metabolism/pathology Autism spectrum disorders Blood-brain barrier Duodenal biopsies Gut permeability Gut-brain axis Neuroinflammation Postmortem brain Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. En ligne : http://dx.doi.org/10.1186/s13229-016-0110-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 The Relationship of Severity of Autism with Gastrointestinal Symptoms and Serum Zonulin Levels in Autistic Children / S. KARAGÖZLÜ in Journal of Autism and Developmental Disorders, 52-2 (February 2022)
[article]
Titre : The Relationship of Severity of Autism with Gastrointestinal Symptoms and Serum Zonulin Levels in Autistic Children Type de document : Texte imprimé et/ou numérique Auteurs : S. KARAGÖZLÜ, Auteur ; B. DALGIÇ, Auteur ; E. ??ERI, Auteur Article en page(s) : p.623-629 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder Autistic Disorder/diagnosis Child Haptoglobins Humans Permeability Protein Precursors Autism spectrum disorder Gastrointestinal symptom Zonulin Index. décimale : PER Périodiques Résumé : To evaluate the relationship between the severity of autism, severity of gastrointestinal symptoms and serum zonulin levels as a marker of increased intestinal permeability in children. Serum zonulin levels were determined in 56 children with ASDs and 55 healthy children. The severity of gastrointestinal symptoms and ASD symptoms was assessed with the Gastrointestinal Symptom Rating Scale (GSRS) and Childhood Autism Rating Scale (CARS), respectively. Serum zonulin levels were significantly higher than healthy controls in children with severe autism. A positive correlation was found between the CARS score, GSRS score and serum zonulin levels (r?=?; P?.001). Our findings suggest that the severity of gastrointestinal symptoms and severity of autism might be related to increased intestinal permeability in ASDs children. En ligne : http://dx.doi.org/10.1007/s10803-021-04966-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455
in Journal of Autism and Developmental Disorders > 52-2 (February 2022) . - p.623-629[article] The Relationship of Severity of Autism with Gastrointestinal Symptoms and Serum Zonulin Levels in Autistic Children [Texte imprimé et/ou numérique] / S. KARAGÖZLÜ, Auteur ; B. DALGIÇ, Auteur ; E. ??ERI, Auteur . - p.623-629.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 52-2 (February 2022) . - p.623-629
Mots-clés : Autism Spectrum Disorder Autistic Disorder/diagnosis Child Haptoglobins Humans Permeability Protein Precursors Autism spectrum disorder Gastrointestinal symptom Zonulin Index. décimale : PER Périodiques Résumé : To evaluate the relationship between the severity of autism, severity of gastrointestinal symptoms and serum zonulin levels as a marker of increased intestinal permeability in children. Serum zonulin levels were determined in 56 children with ASDs and 55 healthy children. The severity of gastrointestinal symptoms and ASD symptoms was assessed with the Gastrointestinal Symptom Rating Scale (GSRS) and Childhood Autism Rating Scale (CARS), respectively. Serum zonulin levels were significantly higher than healthy controls in children with severe autism. A positive correlation was found between the CARS score, GSRS score and serum zonulin levels (r?=?; P?.001). Our findings suggest that the severity of gastrointestinal symptoms and severity of autism might be related to increased intestinal permeability in ASDs children. En ligne : http://dx.doi.org/10.1007/s10803-021-04966-1 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455