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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 Brain region-specific altered expression and association of mitochondria-related genes in autism / Ayyappan ANITHA in Molecular Autism, (November 2012)
[article]
Titre : Brain region-specific altered expression and association of mitochondria-related genes in autism Type de document : Texte imprimé et/ou numérique Auteurs : Ayyappan ANITHA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Ismail THANSEEM, Auteur ; Kazuo YAMADA, Auteur ; Yoshimi IWAYAMA, Auteur ; Tomoko TOYOTA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Satoru YAMADA, Auteur ; Masatsugu TSUJII, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Hironobu ICHIKAWA, Auteur ; Toshiro SUGIYAMA, Auteur ; Takeo YOSHIKAWA, Auteur ; Norio MORI, Auteur Année de publication : 2012 Article en page(s) : 12 p. Langues : Anglais (eng) Mots-clés : Autism Mitochondria Postmortem brain NEFL Uncoupling protein Metaxin Index. décimale : PER Périodiques Résumé : BACKGROUND:Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions.METHODS:For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct ([increment][increment]Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism.RESULTS:Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients.CONCLUSIONS:Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. En ligne : http://dx.doi.org/10.1186/2040-2392-3-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202
in Molecular Autism > (November 2012) . - 12 p.[article] Brain region-specific altered expression and association of mitochondria-related genes in autism [Texte imprimé et/ou numérique] / Ayyappan ANITHA, Auteur ; Kazuhiko NAKAMURA, Auteur ; Ismail THANSEEM, Auteur ; Kazuo YAMADA, Auteur ; Yoshimi IWAYAMA, Auteur ; Tomoko TOYOTA, Auteur ; Hideo MATSUZAKI, Auteur ; Taishi MIYACHI, Auteur ; Satoru YAMADA, Auteur ; Masatsugu TSUJII, Auteur ; Kenji J. TSUCHIYA, Auteur ; Kaori MATSUMOTO, Auteur ; Yasuhide IWATA, Auteur ; Katsuaki SUZUKI, Auteur ; Hironobu ICHIKAWA, Auteur ; Toshiro SUGIYAMA, Auteur ; Takeo YOSHIKAWA, Auteur ; Norio MORI, Auteur . - 2012 . - 12 p.
Langues : Anglais (eng)
in Molecular Autism > (November 2012) . - 12 p.
Mots-clés : Autism Mitochondria Postmortem brain NEFL Uncoupling protein Metaxin Index. décimale : PER Périodiques Résumé : BACKGROUND:Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions.METHODS:For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct ([increment][increment]Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism.RESULTS:Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients.CONCLUSIONS:Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. En ligne : http://dx.doi.org/10.1186/2040-2392-3-12 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=202