Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders / Maria FIORENTINO in Molecular Autism, 7 (2016)  

Public ISBD [article]  inMolecular Autism > 7 (2016) . - 49p. Titre : Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders Type de document : texte imprimé Auteurs : Maria FIORENTINO, Auteur ; Anna SAPONE, Auteur ; Stefania SENGER, Auteur ; Stephanie S. CAMHI, Auteur ; Sarah M. KADZIELSKI, Auteur ; Timothy M. BUIE, Auteur ; Deanna L. KELLY, Auteur ; Nicola CASCELLA, Auteur ; Alessio 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 [article] Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders [texte imprimé] / Maria FIORENTINO, Auteur ; Anna SAPONE, Auteur ; Stefania SENGER, Auteur ; Stephanie S. CAMHI, Auteur ; Sarah M. KADZIELSKI, Auteur ; Timothy M. BUIE, Auteur ; Deanna L. KELLY, Auteur ; Nicola CASCELLA, Auteur ; Alessio 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

Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders / Dario SINISCALCO in Journal of Autism and Developmental Disorders, 43-11 (November 2013)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 43-11 (November 2013) . - p.2686-2695 Titre : Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders Type de document : texte imprimé Auteurs : Dario SINISCALCO, Auteur ; Anna SAPONE, Auteur ; Catia GIORDANO, Auteur ; Alessandra CIRILLO, Auteur ; Laura MAGISTRIS, Auteur ; Francesco ROSSI, Auteur ; Alessio FASANO, Auteur ; James Jeffrey BRADSTREET, Auteur ; Sabatino MAIONE, Auteur ; Nicola ANTONUCCI, Auteur Article en page(s) : p.2686-2695 Langues : Anglais (eng) Mots-clés : Autistic disorders  Cannabinoid system  Gene expression  PBMCs Index. décimale : PER Périodiques Résumé : Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult. Indeed, the treatments for autism presently available can be divided into behavioural, nutritional and medical approaches, although no defined standard approach exists. Autistic children display immune system dysregulation and show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the involvement of cannabinoid system in PBMCs from autistic children compared to age-matched normal healthy developing controls (age ranging 3–9 years; mean age: 6.06 ± 1.52 vs. 6.14 ± 1.39 in autistic children and healthy subjects, respectively). The mRNA level for cannabinoid receptor type 2 (CB2) was significantly increased in AD-PBMCs as compared to healthy subjects (mean ± SE of arbitrary units: 0.34 ± 0.03 vs. 0.23 ± 0.02 in autistic children and healthy subjects, respectively), whereas CB1 and fatty acid amide hydrolase mRNA levels were unchanged. mRNA levels of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D gene were slightly decreased. Protein levels of CB-2 were also significantly increased in autistic children (mean ± SE of arbitrary units: 33.5 ± 1.32 vs. 6.70 ± 1.25 in autistic children and healthy subjects, respectively). Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care. En ligne : http://dx.doi.org/10.1007/s10803-013-1824-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=217 [article] Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders [texte imprimé] / Dario SINISCALCO, Auteur ; Anna SAPONE, Auteur ; Catia GIORDANO, Auteur ; Alessandra CIRILLO, Auteur ; Laura MAGISTRIS, Auteur ; Francesco ROSSI, Auteur ; Alessio FASANO, Auteur ; James Jeffrey BRADSTREET, Auteur ; Sabatino MAIONE, Auteur ; Nicola ANTONUCCI, Auteur . - p.2686-2695. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 43-11 (November 2013) . - p.2686-2695 Mots-clés : Autistic disorders  Cannabinoid system  Gene expression  PBMCs Index. décimale : PER Périodiques Résumé : Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult. Indeed, the treatments for autism presently available can be divided into behavioural, nutritional and medical approaches, although no defined standard approach exists. Autistic children display immune system dysregulation and show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the involvement of cannabinoid system in PBMCs from autistic children compared to age-matched normal healthy developing controls (age ranging 3–9 years; mean age: 6.06 ± 1.52 vs. 6.14 ± 1.39 in autistic children and healthy subjects, respectively). The mRNA level for cannabinoid receptor type 2 (CB2) was significantly increased in AD-PBMCs as compared to healthy subjects (mean ± SE of arbitrary units: 0.34 ± 0.03 vs. 0.23 ± 0.02 in autistic children and healthy subjects, respectively), whereas CB1 and fatty acid amide hydrolase mRNA levels were unchanged. mRNA levels of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D gene were slightly decreased. Protein levels of CB-2 were also significantly increased in autistic children (mean ± SE of arbitrary units: 33.5 ± 1.32 vs. 6.70 ± 1.25 in autistic children and healthy subjects, respectively). Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care. En ligne : http://dx.doi.org/10.1007/s10803-013-1824-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=217

The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients / Dario SINISCALCO in Journal of Autism and Developmental Disorders, 42-7 (July 2012)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 42-7 (July 2012) . - p.1403-1410 Titre : The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients Type de document : texte imprimé Auteurs : Dario SINISCALCO, Auteur ; Anna SAPONE, Auteur ; Catia GIORDANO, Auteur ; Alessandra CIRILLO, Auteur ; Vito DE NOVELLIS, Auteur ; Laura DE MAGISTRIS, Auteur ; Francesco ROSSI, Auteur ; Alessio FASANO, Auteur ; Sabatino SABATINO, Auteur ; Nicola ANTONUCCI, Auteur Année de publication : 2012 Article en page(s) : p.1403-1410 Langues : Anglais (eng) Mots-clés : Autism spectrum disorders  Caspases  Gene expression  PBMCs Index. décimale : PER Périodiques Résumé : Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro-developmental disorders characterized by dysfunctions in social interaction and communication skills. Their pathogenesis has been linked to interactions between genes and environmental factors. Consistent with the evidence of certain similarities between immune cells and neurons, autistic children also show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the activation of caspases, cysteinyl aspartate-specific proteases involved in apoptosis and several other cell functions in PBMCs from 15 ASD children compared to age-matched normal healthy developing controls. The mRNA levels for caspase-1, -2, -4, -5 were significantly increased in ASD children as compared to healthy subjects. Protein levels of Caspase-3, -7, -12 were also increased in ASD patients. Our data are suggestive of a possible role of the capsase pathway in ASD clinical outcome and of the use of caspase as potential diagnostic and/or therapeutic tools in ASD management. En ligne : http://dx.doi.org/10.1007/s10803-011-1373-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=166 [article] The Expression of Caspases is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients [texte imprimé] / Dario SINISCALCO, Auteur ; Anna SAPONE, Auteur ; Catia GIORDANO, Auteur ; Alessandra CIRILLO, Auteur ; Vito DE NOVELLIS, Auteur ; Laura DE MAGISTRIS, Auteur ; Francesco ROSSI, Auteur ; Alessio FASANO, Auteur ; Sabatino SABATINO, Auteur ; Nicola ANTONUCCI, Auteur . - 2012 . - p.1403-1410. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 42-7 (July 2012) . - p.1403-1410 Mots-clés : Autism spectrum disorders  Caspases  Gene expression  PBMCs Index. décimale : PER Périodiques Résumé : Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro-developmental disorders characterized by dysfunctions in social interaction and communication skills. Their pathogenesis has been linked to interactions between genes and environmental factors. Consistent with the evidence of certain similarities between immune cells and neurons, autistic children also show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the activation of caspases, cysteinyl aspartate-specific proteases involved in apoptosis and several other cell functions in PBMCs from 15 ASD children compared to age-matched normal healthy developing controls. The mRNA levels for caspase-1, -2, -4, -5 were significantly increased in ASD children as compared to healthy subjects. Protein levels of Caspase-3, -7, -12 were also increased in ASD patients. Our data are suggestive of a possible role of the capsase pathway in ASD clinical outcome and of the use of caspase as potential diagnostic and/or therapeutic tools in ASD management. En ligne : http://dx.doi.org/10.1007/s10803-011-1373-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=166

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