Colonic dilation and altered ex vivo gastrointestinal motility in the neuroligin-3 knockout mouse / Anita J. L. LEEMBRUGGEN in Autism Research, 13-5 (May 2020)  

Public ISBD [article]  inAutism Research > 13-5 (May 2020) . - p.691-701 Titre : Colonic dilation and altered ex vivo gastrointestinal motility in the neuroligin-3 knockout mouse Type de document : Texte imprimé et/ou numérique Auteurs : Anita J. L. LEEMBRUGGEN, Auteur ; Gayathri K. BALASURIYA, Auteur ; Jinghong ZHANG, Auteur ; Shana SCHOKMAN, Auteur ; Kristy SWIDERSKI, Auteur ; Joel C. BORNSTEIN, Auteur ; Jess NITHIANANTHARAJAH, Auteur ; Elisa L. HILL-YARDIN, Auteur Article en page(s) : p.691-701 Langues : Anglais (eng) Mots-clés : Neuroligin-3  autism  gastrointestinal symptoms  gut motility  immunofluorescence  mouse models Index. décimale : PER Périodiques Résumé : Gastrointestinal (GI) dysfunction is commonly reported by people diagnosed with autism spectrum disorder (ASD; autism) but the cause is unknown. Mutations in genes encoding synaptic proteins including Neuroligin-3 are associated with autism. Mice lacking Neuroligin-3 (Nlgn3(-/-) ) have altered brain function, but whether the enteric nervous system (ENS) is altered remains unknown. We assessed for changes in GI structure and function in Nlgn3(-/-) mice. We found no significant morphological differences in villus height or crypt depth in the jejunum or colon between wildtype (WT) and Nlgn3(-/-) mice. To determine whether deletion of Nlgn3 affects enteric neurons, we stained for neural markers in the myenteric plexus. Nlgn3(-/-) mice had similar numbers of neurons expressing the pan-neuronal marker Hu in the jejunum, proximal mid, and distal colon regions. We also found no differences in the number of neuronal nitric oxide synthase (nNOS+) or calretinin (CalR+) motor neurons and interneurons between WT and Nlgn3(-/-) mice. We used ex vivo video imaging analysis to assess colonic motility under baseline conditions and observed faster colonic migrating motor complexes (CMMCs) and an increased colonic diameter in Nlgn3(-/-) mice, although CMMC frequency was unchanged. At baseline, CMMCs were faster in Nlgn3(-/-) mice compared to WT. Although the numbers of neuronal subsets are conserved in Nlgn3(-/-) mice, these findings suggest that Neuroligin-3 modulates inhibitory neural pathways in the ENS and may contribute to mechanisms underlying GI disorders in autism. Autism Res 2020, 13: 691-701. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: People with autism commonly experience gut problems. Many gene mutations associated with autism affect neuronal activity. We studied mice in which the autism-associated Neuroligin-3 gene is deleted to determine whether this impacts gut neuronal numbers or motility. We found that although mutant mice had similar gut structure and numbers of neurons in all gut regions examined, they had distended colons and faster colonic muscle contractions. Further work is needed to understand how Neuroligin-3 affects neuron connectivity in the gastrointestinal tract. En ligne : http://dx.doi.org/10.1002/aur.2109 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=422 [article] Colonic dilation and altered ex vivo gastrointestinal motility in the neuroligin-3 knockout mouse [Texte imprimé et/ou numérique] / Anita J. L. LEEMBRUGGEN, Auteur ; Gayathri K. BALASURIYA, Auteur ; Jinghong ZHANG, Auteur ; Shana SCHOKMAN, Auteur ; Kristy SWIDERSKI, Auteur ; Joel C. BORNSTEIN, Auteur ; Jess NITHIANANTHARAJAH, Auteur ; Elisa L. HILL-YARDIN, Auteur . - p.691-701. Langues : Anglais (eng) in Autism Research > 13-5 (May 2020) . - p.691-701 Mots-clés : Neuroligin-3  autism  gastrointestinal symptoms  gut motility  immunofluorescence  mouse models Index. décimale : PER Périodiques Résumé : Gastrointestinal (GI) dysfunction is commonly reported by people diagnosed with autism spectrum disorder (ASD; autism) but the cause is unknown. Mutations in genes encoding synaptic proteins including Neuroligin-3 are associated with autism. Mice lacking Neuroligin-3 (Nlgn3(-/-) ) have altered brain function, but whether the enteric nervous system (ENS) is altered remains unknown. We assessed for changes in GI structure and function in Nlgn3(-/-) mice. We found no significant morphological differences in villus height or crypt depth in the jejunum or colon between wildtype (WT) and Nlgn3(-/-) mice. To determine whether deletion of Nlgn3 affects enteric neurons, we stained for neural markers in the myenteric plexus. Nlgn3(-/-) mice had similar numbers of neurons expressing the pan-neuronal marker Hu in the jejunum, proximal mid, and distal colon regions. We also found no differences in the number of neuronal nitric oxide synthase (nNOS+) or calretinin (CalR+) motor neurons and interneurons between WT and Nlgn3(-/-) mice. We used ex vivo video imaging analysis to assess colonic motility under baseline conditions and observed faster colonic migrating motor complexes (CMMCs) and an increased colonic diameter in Nlgn3(-/-) mice, although CMMC frequency was unchanged. At baseline, CMMCs were faster in Nlgn3(-/-) mice compared to WT. Although the numbers of neuronal subsets are conserved in Nlgn3(-/-) mice, these findings suggest that Neuroligin-3 modulates inhibitory neural pathways in the ENS and may contribute to mechanisms underlying GI disorders in autism. Autism Res 2020, 13: 691-701. (c) 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: People with autism commonly experience gut problems. Many gene mutations associated with autism affect neuronal activity. We studied mice in which the autism-associated Neuroligin-3 gene is deleted to determine whether this impacts gut neuronal numbers or motility. We found that although mutant mice had similar gut structure and numbers of neurons in all gut regions examined, they had distended colons and faster colonic muscle contractions. Further work is needed to understand how Neuroligin-3 affects neuron connectivity in the gastrointestinal tract. En ligne : http://dx.doi.org/10.1002/aur.2109 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=422

Gastrointestinal dysfunction in patients and mice expressing the autism-associated R451C mutation in neuroligin-3 / S. HOSIE in Autism Research, 12-7 (July 2019)  

Public ISBD [article]  inAutism Research > 12-7 (July 2019) . - p.1043-1056 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 [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

A neuroligin-3 mutation implicated in autism causes abnormal aggression and increases repetitive behavior in mice / Emma L. BURROWS in Molecular Autism, (November 2015)  

Public ISBD [article]  inMolecular Autism > (November 2015) . - p.1-11 Titre : A neuroligin-3 mutation implicated in autism causes abnormal aggression and increases repetitive behavior in mice Type de document : Texte imprimé et/ou numérique Auteurs : Emma L. BURROWS, Auteur ; Liliana LASKARIS, Auteur ; Lynn KOYAMA, Auteur ; Leonid CHURILOV, Auteur ; Joel C. BORNSTEIN, Auteur ; Elisa L. HILL-YARDIN, Auteur ; Anthony J. HANNAN, Auteur Article en page(s) : p.1-11 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Aggression is common in patients with autism spectrum disorders (ASD) along with the core symptoms of impairments in social communication and repetitive behavior. Risperidone, an atypical antipsychotic, is widely used to treat aggression in ASD. In order to understand the neurobiological underpinnings of these challenging behaviors, a thorough characterisation of behavioral endophenotypes in animal models is required. En ligne : http://dx.doi.org/10.1186/s13229-015-0055-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=277 [article] A neuroligin-3 mutation implicated in autism causes abnormal aggression and increases repetitive behavior in mice [Texte imprimé et/ou numérique] / Emma L. BURROWS, Auteur ; Liliana LASKARIS, Auteur ; Lynn KOYAMA, Auteur ; Leonid CHURILOV, Auteur ; Joel C. BORNSTEIN, Auteur ; Elisa L. HILL-YARDIN, Auteur ; Anthony J. HANNAN, Auteur . - p.1-11. Langues : Anglais (eng) in Molecular Autism > (November 2015) . - p.1-11 Index. décimale : PER Périodiques Résumé : Aggression is common in patients with autism spectrum disorders (ASD) along with the core symptoms of impairments in social communication and repetitive behavior. Risperidone, an atypical antipsychotic, is widely used to treat aggression in ASD. In order to understand the neurobiological underpinnings of these challenging behaviors, a thorough characterisation of behavioral endophenotypes in animal models is required. En ligne : http://dx.doi.org/10.1186/s13229-015-0055-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=277

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