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Auteur Tor SAVIDGE |
Documents disponibles écrits par cet auteur (2)
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Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3 / S. HOSIE in Autism Research, 12-7 (July 2019)
[article]
Titre : Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3 Type de document : Texte imprimé et/ou numérique Auteurs : S. HOSIE, Auteur ; M. ELLIS, Auteur ; M. SWAMINATHAN, Auteur ; F. RAMALHOSA, Auteur ; G. O. SEGER, Auteur ; Gayathri K. BALASURIYA, Auteur ; C. GILLBERG, Auteur ; M. RASTAM, Auteur ; L. CHURILOV, Auteur ; S. J. MCKEOWN, Auteur ; N. YALCINKAYA, Auteur ; P. URVIL, Auteur ; Tor SAVIDGE, Auteur ; C. A. BELL, Auteur ; O. BODIN, Auteur ; J. WOOD, Auteur ; A. E. FRANKS, Auteur ; Joel C. BORNSTEIN, Auteur ; E. L. HILL-YARDIN, Auteur Année de publication : 2019 Article en page(s) : p.1043-1056 Langues : Anglais (eng) Mots-clés : autism gastrointestinal symptoms gut motility immunofluorescence mouse neuroligin-3 Index. décimale : PER Périodiques Résumé : Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brothers with autism and an R451C mutation in Nlgn3 encoding the synaptic adhesion protein, neuroligin-3. We confirm the presence of an array of synaptic genes in the murine GI tract and investigate the impact of impaired synaptic protein expression in mice carrying the human neuroligin-3 R451C missense mutation (NL3(R451C) ). Assessing in vivo gut dysfunction, we report faster small intestinal transit in NL3(R451C) compared to wild-type mice. Using an ex vivo colonic motility assay, we show increased sensitivity to GABAA receptor modulation in NL3(R451C) mice, a well-established Central Nervous System (CNS) feature associated with this mutation. We further show increased numbers of small intestine myenteric neurons in NL3(R451C) mice. Although we observed altered sensitivity to GABAA receptor modulators in the colon, there was no change in colonic neuronal numbers including the number of GABA-immunoreactive myenteric neurons. We further identified altered fecal microbial communities in NL3(R451C) mice. These results suggest that the R451C mutation affects small intestinal and colonic function and alter neuronal numbers in the small intestine as well as impact fecal microbes. Our findings identify a novel GI phenotype associated with the R451C mutation and highlight NL3(R451C) mice as a useful preclinical model of GI dysfunction in autism. Autism Res 2019, 12: 1043-1056. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism commonly experience gastrointestinal problems, however the cause is unknown. We report gut symptoms in patients with the autism-associated R451C mutation encoding the neuroligin-3 protein. We show that many of the genes implicated in autism are expressed in mouse gut. The neuroligin-3 R451C mutation alters the enteric nervous system, causes gastrointestinal dysfunction, and disrupts gut microbe populations in mice. Gut dysfunction in autism could be due to mutations that affect neuronal communication. En ligne : http://dx.doi.org/10.1002/aur.2127 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402
in Autism Research > 12-7 (July 2019) . - p.1043-1056[article] Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3 [Texte imprimé et/ou numérique] / S. HOSIE, Auteur ; M. ELLIS, Auteur ; M. SWAMINATHAN, Auteur ; F. RAMALHOSA, Auteur ; G. O. SEGER, Auteur ; Gayathri K. BALASURIYA, Auteur ; C. GILLBERG, Auteur ; M. RASTAM, Auteur ; L. CHURILOV, Auteur ; S. J. MCKEOWN, Auteur ; N. YALCINKAYA, Auteur ; P. URVIL, Auteur ; Tor SAVIDGE, Auteur ; C. A. BELL, Auteur ; O. BODIN, Auteur ; J. WOOD, Auteur ; A. E. FRANKS, Auteur ; Joel C. BORNSTEIN, Auteur ; E. L. HILL-YARDIN, Auteur . - 2019 . - p.1043-1056.
Langues : Anglais (eng)
in Autism Research > 12-7 (July 2019) . - p.1043-1056
Mots-clés : autism gastrointestinal symptoms gut motility immunofluorescence mouse neuroligin-3 Index. décimale : PER Périodiques Résumé : Gastrointestinal (GI) problems constitute an important comorbidity in many patients with autism. Multiple mutations in the neuroligin family of synaptic adhesion molecules are implicated in autism, however whether they are expressed and impact GI function via changes in the enteric nervous system is unknown. We report the GI symptoms of two brothers with autism and an R451C mutation in Nlgn3 encoding the synaptic adhesion protein, neuroligin-3. We confirm the presence of an array of synaptic genes in the murine GI tract and investigate the impact of impaired synaptic protein expression in mice carrying the human neuroligin-3 R451C missense mutation (NL3(R451C) ). Assessing in vivo gut dysfunction, we report faster small intestinal transit in NL3(R451C) compared to wild-type mice. Using an ex vivo colonic motility assay, we show increased sensitivity to GABAA receptor modulation in NL3(R451C) mice, a well-established Central Nervous System (CNS) feature associated with this mutation. We further show increased numbers of small intestine myenteric neurons in NL3(R451C) mice. Although we observed altered sensitivity to GABAA receptor modulators in the colon, there was no change in colonic neuronal numbers including the number of GABA-immunoreactive myenteric neurons. We further identified altered fecal microbial communities in NL3(R451C) mice. These results suggest that the R451C mutation affects small intestinal and colonic function and alter neuronal numbers in the small intestine as well as impact fecal microbes. Our findings identify a novel GI phenotype associated with the R451C mutation and highlight NL3(R451C) mice as a useful preclinical model of GI dysfunction in autism. Autism Res 2019, 12: 1043-1056. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism commonly experience gastrointestinal problems, however the cause is unknown. We report gut symptoms in patients with the autism-associated R451C mutation encoding the neuroligin-3 protein. We show that many of the genes implicated in autism are expressed in mouse gut. The neuroligin-3 R451C mutation alters the enteric nervous system, causes gastrointestinal dysfunction, and disrupts gut microbe populations in mice. Gut dysfunction in autism could be due to mutations that affect neuronal communication. En ligne : http://dx.doi.org/10.1002/aur.2127 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=402 Intestinal Predictors of Whole Blood Serotonin Levels in Children With or Without Autism / Miranda ZUNIGA-KENNEDY in Journal of Autism and Developmental Disorders, 52-9 (September 2022)
[article]
Titre : Intestinal Predictors of Whole Blood Serotonin Levels in Children With or Without Autism Type de document : Texte imprimé et/ou numérique Auteurs : Miranda ZUNIGA-KENNEDY, Auteur ; Micah DAVOREN, Auteur ; Lauren C. SHUFFREY, Auteur ; Ruth Ann LUNA, Auteur ; Tor SAVIDGE, Auteur ; Vinay PRASAD, Auteur ; George M. ANDERSON, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur ; Kent C. WILLIAMS, Auteur Article en page(s) : p.3780-3789 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/genetics Autistic Disorder/genetics Biomarkers Child Humans Male Serotonin Autism Hyperserotonemia Immunity Whole blood serotonin Index. décimale : PER Périodiques Résumé : Hyperserotonemia, or elevated levels of whole blood serotonin (WB5-HT), was the first biomarker linked to autism spectrum disorder (ASD). Despite numerous studies investigating the etiology of hyperserotonemia, results have been inconsistent. Recent findings suggest a relationship between the immune system and hyperserotonemia. The current study investigated whether intestinal 5-HT levels, 5-HT gene expression, or intestinal cell types predict WB5-HT. Participants included thirty-one males aged 3-18 who were classified into one of three groups: ASD and functional GI issues, typically developing with GI issues, and typically developing without GI issues. Samples from a lower endoscopy were analyzed to examine the pathways in predicting WB-5HT. Results demonstrated an association between T-Lymphocytes and WB5-HT. En ligne : http://dx.doi.org/10.1007/s10803-022-05597-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=485
in Journal of Autism and Developmental Disorders > 52-9 (September 2022) . - p.3780-3789[article] Intestinal Predictors of Whole Blood Serotonin Levels in Children With or Without Autism [Texte imprimé et/ou numérique] / Miranda ZUNIGA-KENNEDY, Auteur ; Micah DAVOREN, Auteur ; Lauren C. SHUFFREY, Auteur ; Ruth Ann LUNA, Auteur ; Tor SAVIDGE, Auteur ; Vinay PRASAD, Auteur ; George M. ANDERSON, Auteur ; Jeremy VEENSTRA-VANDERWEELE, Auteur ; Kent C. WILLIAMS, Auteur . - p.3780-3789.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 52-9 (September 2022) . - p.3780-3789
Mots-clés : Autism Spectrum Disorder/genetics Autistic Disorder/genetics Biomarkers Child Humans Male Serotonin Autism Hyperserotonemia Immunity Whole blood serotonin Index. décimale : PER Périodiques Résumé : Hyperserotonemia, or elevated levels of whole blood serotonin (WB5-HT), was the first biomarker linked to autism spectrum disorder (ASD). Despite numerous studies investigating the etiology of hyperserotonemia, results have been inconsistent. Recent findings suggest a relationship between the immune system and hyperserotonemia. The current study investigated whether intestinal 5-HT levels, 5-HT gene expression, or intestinal cell types predict WB5-HT. Participants included thirty-one males aged 3-18 who were classified into one of three groups: ASD and functional GI issues, typically developing with GI issues, and typically developing without GI issues. Samples from a lower endoscopy were analyzed to examine the pathways in predicting WB-5HT. Results demonstrated an association between T-Lymphocytes and WB5-HT. En ligne : http://dx.doi.org/10.1007/s10803-022-05597-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=485