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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 An elevated anxiety level among prepubertal autistic boys with non-treatment-seeking functional gastrointestinal disorders: A case-control study / O. W. H. WONG in Autism Research, 14-10 (October 2021)
[article]
Titre : An elevated anxiety level among prepubertal autistic boys with non-treatment-seeking functional gastrointestinal disorders: A case-control study Type de document : Texte imprimé et/ou numérique Auteurs : O. W. H. WONG, Auteur ; A. M. W. LAM, Auteur ; Kelly Y. C. LAI, Auteur ; S. L. MA, Auteur ; S. F. HUNG, Auteur ; S. CHAN, Auteur ; S. WONG, Auteur ; P. W. L. LEUNG, Auteur Article en page(s) : p.2131-2142 Langues : Anglais (eng) Mots-clés : Anxiety/complications Autism Spectrum Disorder/complications/epidemiology Autistic Disorder/complications/epidemiology Case-Control Studies Child Child, Preschool Gastrointestinal Diseases/complications/epidemiology Humans Male abdominal pain anxiety autism constipation functional gastrointestinal disorder gut-brain axis nausea Index. décimale : PER Périodiques Résumé : Children with autism commonly suffer from comorbid functional gastrointestinal disorders (FGID) and anxiety. The raised prevalence of both conditions in autism suggests complex reciprocal relationships, which are seldom explored in non-treatment-seeking FGID. The relationships between subtypes of FGID and anxiety are also unclear. This study recruited boys with autism and age-matched typically developing (TD) boys, aged 4-11?years, who were not actively seeking help for gastrointestinal problems. Their parents completed the Rome IV Diagnostic Questionnaires for Pediatric FGID. Four groups of children with and without autism/FGID were identified and compared on their anxiety level using the Spence children's anxiety scale. In 69 boys with autism and 69 age-matched TD boys, FGID were identified in 22 and 16 boys, respectively. ANCOVA demonstrated a significant interaction effect of autism and FGID on anxiety (F[1, 129] = 5.43, p = 0.021), while conditional logistic regression identified an interaction effect of autism and anxiety on the odds of FGID (OR 1.038, 95% CI 1.002-1.075, p = 0.038). Explorative post hoc analysis showed higher anxiety in functional nausea and vomiting disorder (p = 0.033) and functional abdominal pain disorder (p = 0.029) among boys with autism than TD boys with the same respective subtypes of FGID. In summary, among prepubertal boys with autism, the presence of FGID that are non-treatment-seeking in nature, has a significantly stronger association with higher levels of anxiety than TD boys. The strength of association may be more prominent in subtypes of FGID. Possible pathomechanisms including the underlying microbiota spectra and inflammatory paths should be explored in future studies. LAY SUMMARY: Anxiety and gastrointestinal problems are common symptoms in autism. Given that gut health could be linked to emotions, their association in young boys with autism was studied. The presence of nausea vomiting, or abdominal pain were associated with raised anxiety among boys with autism, yet this was not observed in typically developing boys. This suggests that anxiety among autistic children could be partly explained by the presence of FGID. En ligne : http://dx.doi.org/10.1002/aur.2555 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450
in Autism Research > 14-10 (October 2021) . - p.2131-2142[article] An elevated anxiety level among prepubertal autistic boys with non-treatment-seeking functional gastrointestinal disorders: A case-control study [Texte imprimé et/ou numérique] / O. W. H. WONG, Auteur ; A. M. W. LAM, Auteur ; Kelly Y. C. LAI, Auteur ; S. L. MA, Auteur ; S. F. HUNG, Auteur ; S. CHAN, Auteur ; S. WONG, Auteur ; P. W. L. LEUNG, Auteur . - p.2131-2142.
Langues : Anglais (eng)
in Autism Research > 14-10 (October 2021) . - p.2131-2142
Mots-clés : Anxiety/complications Autism Spectrum Disorder/complications/epidemiology Autistic Disorder/complications/epidemiology Case-Control Studies Child Child, Preschool Gastrointestinal Diseases/complications/epidemiology Humans Male abdominal pain anxiety autism constipation functional gastrointestinal disorder gut-brain axis nausea Index. décimale : PER Périodiques Résumé : Children with autism commonly suffer from comorbid functional gastrointestinal disorders (FGID) and anxiety. The raised prevalence of both conditions in autism suggests complex reciprocal relationships, which are seldom explored in non-treatment-seeking FGID. The relationships between subtypes of FGID and anxiety are also unclear. This study recruited boys with autism and age-matched typically developing (TD) boys, aged 4-11?years, who were not actively seeking help for gastrointestinal problems. Their parents completed the Rome IV Diagnostic Questionnaires for Pediatric FGID. Four groups of children with and without autism/FGID were identified and compared on their anxiety level using the Spence children's anxiety scale. In 69 boys with autism and 69 age-matched TD boys, FGID were identified in 22 and 16 boys, respectively. ANCOVA demonstrated a significant interaction effect of autism and FGID on anxiety (F[1, 129] = 5.43, p = 0.021), while conditional logistic regression identified an interaction effect of autism and anxiety on the odds of FGID (OR 1.038, 95% CI 1.002-1.075, p = 0.038). Explorative post hoc analysis showed higher anxiety in functional nausea and vomiting disorder (p = 0.033) and functional abdominal pain disorder (p = 0.029) among boys with autism than TD boys with the same respective subtypes of FGID. In summary, among prepubertal boys with autism, the presence of FGID that are non-treatment-seeking in nature, has a significantly stronger association with higher levels of anxiety than TD boys. The strength of association may be more prominent in subtypes of FGID. Possible pathomechanisms including the underlying microbiota spectra and inflammatory paths should be explored in future studies. LAY SUMMARY: Anxiety and gastrointestinal problems are common symptoms in autism. Given that gut health could be linked to emotions, their association in young boys with autism was studied. The presence of nausea vomiting, or abdominal pain were associated with raised anxiety among boys with autism, yet this was not observed in typically developing boys. This suggests that anxiety among autistic children could be partly explained by the presence of FGID. En ligne : http://dx.doi.org/10.1002/aur.2555 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450