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Auteur I. SCHNEIDER |
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Loss of the Chr16p11.2 ASD candidate gene QPRT leads to aberrant neuronal differentiation in the SH-SY5Y neuronal cell model / D. HASLINGER in Molecular Autism, 9 (2018)
[article]
Titre : Loss of the Chr16p11.2 ASD candidate gene QPRT leads to aberrant neuronal differentiation in the SH-SY5Y neuronal cell model Type de document : Texte imprimé et/ou numérique Auteurs : D. HASLINGER, Auteur ; R. WALTES, Auteur ; A. YOUSAF, Auteur ; S. LINDLAR, Auteur ; I. SCHNEIDER, Auteur ; C. K. LIM, Auteur ; M. M. TSAI, Auteur ; B. K. GARVALOV, Auteur ; A. ACKER-PALMER, Auteur ; N. KREZDORN, Auteur ; B. ROTTER, Auteur ; T. ACKER, Auteur ; G. J. GUILLEMIN, Auteur ; S. FULDA, Auteur ; C. M. FREITAG, Auteur ; Andreas G. CHIOCCHETTI, Auteur Article en page(s) : 56p. Langues : Anglais (eng) Mots-clés : 16p11.2 Autism CRISPR/Cas9 Kynurenine Quinolinate phosphoribosyltransferase Quinolinic acid Sholl analysis has been positively reviewed by the ethic's committee Frankfurt (No 267/09).All authors agree to publish the presented work.All authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Altered neuronal development is discussed as the underlying pathogenic mechanism of autism spectrum disorders (ASD). Copy number variations of 16p11.2 have recurrently been identified in individuals with ASD. Of the 29 genes within this region, quinolinate phosphoribosyltransferase (QPRT) showed the strongest regulation during neuronal differentiation of SH-SY5Y neuroblastoma cells. We hypothesized a causal relation between this tryptophan metabolism-related enzyme and neuronal differentiation. We thus analyzed the effect of QPRT on the differentiation of SH-SY5Y and specifically focused on neuronal morphology, metabolites of the tryptophan pathway, and the neurodevelopmental transcriptome. Methods: The gene dosage-dependent change of QPRT expression following Chr16p11.2 deletion was investigated in a lymphoblastoid cell line (LCL) of a deletion carrier and compared to his non-carrier parents. Expression of QPRT was tested for correlation with neuromorphology in SH-SY5Y cells. QPRT function was inhibited in SH-SY5Y neuroblastoma cells using (i) siRNA knockdown (KD), (ii) chemical mimicking of loss of QPRT, and (iii) complete CRISPR/Cas9-mediated knock out (KO). QPRT-KD cells underwent morphological analysis. Chemically inhibited and QPRT-KO cells were characterized using viability assays. Additionally, QPRT-KO cells underwent metabolite and whole transcriptome analyses. Genes differentially expressed upon KO of QPRT were tested for enrichment in biological processes and co-regulated gene-networks of the human brain. Results: QPRT expression was reduced in the LCL of the deletion carrier and significantly correlated with the neuritic complexity of SH-SY5Y. The reduction of QPRT altered neuronal morphology of differentiated SH-SY5Y cells. Chemical inhibition as well as complete KO of the gene were lethal upon induction of neuronal differentiation, but not proliferation. The QPRT-associated tryptophan pathway was not affected by KO. At the transcriptome level, genes linked to neurodevelopmental processes and synaptic structures were affected. Differentially regulated genes were enriched for ASD candidates, and co-regulated gene networks were implicated in the development of the dorsolateral prefrontal cortex, the hippocampus, and the amygdala. Conclusions: In this study, QPRT was causally related to in vitro neuronal differentiation of SH-SY5Y cells and affected the regulation of genes and gene networks previously implicated in ASD. Thus, our data suggest that QPRT may play an important role in the pathogenesis of ASD in Chr16p11.2 deletion carriers. En ligne : https://dx.doi.org/10.1186/s13229-018-0239-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371
in Molecular Autism > 9 (2018) . - 56p.[article] Loss of the Chr16p11.2 ASD candidate gene QPRT leads to aberrant neuronal differentiation in the SH-SY5Y neuronal cell model [Texte imprimé et/ou numérique] / D. HASLINGER, Auteur ; R. WALTES, Auteur ; A. YOUSAF, Auteur ; S. LINDLAR, Auteur ; I. SCHNEIDER, Auteur ; C. K. LIM, Auteur ; M. M. TSAI, Auteur ; B. K. GARVALOV, Auteur ; A. ACKER-PALMER, Auteur ; N. KREZDORN, Auteur ; B. ROTTER, Auteur ; T. ACKER, Auteur ; G. J. GUILLEMIN, Auteur ; S. FULDA, Auteur ; C. M. FREITAG, Auteur ; Andreas G. CHIOCCHETTI, Auteur . - 56p.
Langues : Anglais (eng)
in Molecular Autism > 9 (2018) . - 56p.
Mots-clés : 16p11.2 Autism CRISPR/Cas9 Kynurenine Quinolinate phosphoribosyltransferase Quinolinic acid Sholl analysis has been positively reviewed by the ethic's committee Frankfurt (No 267/09).All authors agree to publish the presented work.All authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Altered neuronal development is discussed as the underlying pathogenic mechanism of autism spectrum disorders (ASD). Copy number variations of 16p11.2 have recurrently been identified in individuals with ASD. Of the 29 genes within this region, quinolinate phosphoribosyltransferase (QPRT) showed the strongest regulation during neuronal differentiation of SH-SY5Y neuroblastoma cells. We hypothesized a causal relation between this tryptophan metabolism-related enzyme and neuronal differentiation. We thus analyzed the effect of QPRT on the differentiation of SH-SY5Y and specifically focused on neuronal morphology, metabolites of the tryptophan pathway, and the neurodevelopmental transcriptome. Methods: The gene dosage-dependent change of QPRT expression following Chr16p11.2 deletion was investigated in a lymphoblastoid cell line (LCL) of a deletion carrier and compared to his non-carrier parents. Expression of QPRT was tested for correlation with neuromorphology in SH-SY5Y cells. QPRT function was inhibited in SH-SY5Y neuroblastoma cells using (i) siRNA knockdown (KD), (ii) chemical mimicking of loss of QPRT, and (iii) complete CRISPR/Cas9-mediated knock out (KO). QPRT-KD cells underwent morphological analysis. Chemically inhibited and QPRT-KO cells were characterized using viability assays. Additionally, QPRT-KO cells underwent metabolite and whole transcriptome analyses. Genes differentially expressed upon KO of QPRT were tested for enrichment in biological processes and co-regulated gene-networks of the human brain. Results: QPRT expression was reduced in the LCL of the deletion carrier and significantly correlated with the neuritic complexity of SH-SY5Y. The reduction of QPRT altered neuronal morphology of differentiated SH-SY5Y cells. Chemical inhibition as well as complete KO of the gene were lethal upon induction of neuronal differentiation, but not proliferation. The QPRT-associated tryptophan pathway was not affected by KO. At the transcriptome level, genes linked to neurodevelopmental processes and synaptic structures were affected. Differentially regulated genes were enriched for ASD candidates, and co-regulated gene networks were implicated in the development of the dorsolateral prefrontal cortex, the hippocampus, and the amygdala. Conclusions: In this study, QPRT was causally related to in vitro neuronal differentiation of SH-SY5Y cells and affected the regulation of genes and gene networks previously implicated in ASD. Thus, our data suggest that QPRT may play an important role in the pathogenesis of ASD in Chr16p11.2 deletion carriers. En ligne : https://dx.doi.org/10.1186/s13229-018-0239-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 Pilot Study of an Attention and Executive Function Cognitive Intervention in Children with Autism Spectrum Disorders / S. J. MACOUN in Journal of Autism and Developmental Disorders, 51-8 (August 2021)
[article]
Titre : Pilot Study of an Attention and Executive Function Cognitive Intervention in Children with Autism Spectrum Disorders Type de document : Texte imprimé et/ou numérique Auteurs : S. J. MACOUN, Auteur ; I. SCHNEIDER, Auteur ; B. BEDIR, Auteur ; J. SHEEHAN, Auteur ; A. SUNG, Auteur Article en page(s) : p.2600-2610 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/therapy Child Cognition Communication Emotional Regulation Executive Function Female Humans Male Parents Pilot Projects Schools Social Skills Attention training Autism Cognitive intervention Executive function training Metacognitive strategy teaching Process specific intervention Index. décimale : PER Périodiques Résumé : This pilot study investigated the efficacy of a game-based cognitive training program (Caribbean Quest; CQ) for improving attention and executive function (EF) in school-aged children with Autism Spectrum Disorder (ASD). CQ is a 'serious game' that uses a hybrid process-specific/compensatory approach to remediate attention and EF abilities through repetitive, hierarchically graded exercises delivered in an adaptive format. Game-play is accompanied by instruction in metacognitive strategies delivered by an adult trainer. Twenty children diagnosed with ASD (ages 6-12 years) completed 12 h of intervention in schools over 8-10 weeks that was facilitated by a trained Research Assistant. Pre-post testing indicated near transfer gains for visual working memory and selective attention and far transfer effects for math fluency. Exit interviews with parents and school staff indicated anecdotal gains in attention, EF, emotion-regulation, flexibility, communication, and social skills. Overall, this study provides preliminary support for the feasibility and potential efficacy of the CQ when delivered in schools to children with ASD. En ligne : http://dx.doi.org/10.1007/s10803-020-04723-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=452
in Journal of Autism and Developmental Disorders > 51-8 (August 2021) . - p.2600-2610[article] Pilot Study of an Attention and Executive Function Cognitive Intervention in Children with Autism Spectrum Disorders [Texte imprimé et/ou numérique] / S. J. MACOUN, Auteur ; I. SCHNEIDER, Auteur ; B. BEDIR, Auteur ; J. SHEEHAN, Auteur ; A. SUNG, Auteur . - p.2600-2610.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 51-8 (August 2021) . - p.2600-2610
Mots-clés : Autism Spectrum Disorder/therapy Child Cognition Communication Emotional Regulation Executive Function Female Humans Male Parents Pilot Projects Schools Social Skills Attention training Autism Cognitive intervention Executive function training Metacognitive strategy teaching Process specific intervention Index. décimale : PER Périodiques Résumé : This pilot study investigated the efficacy of a game-based cognitive training program (Caribbean Quest; CQ) for improving attention and executive function (EF) in school-aged children with Autism Spectrum Disorder (ASD). CQ is a 'serious game' that uses a hybrid process-specific/compensatory approach to remediate attention and EF abilities through repetitive, hierarchically graded exercises delivered in an adaptive format. Game-play is accompanied by instruction in metacognitive strategies delivered by an adult trainer. Twenty children diagnosed with ASD (ages 6-12 years) completed 12 h of intervention in schools over 8-10 weeks that was facilitated by a trained Research Assistant. Pre-post testing indicated near transfer gains for visual working memory and selective attention and far transfer effects for math fluency. Exit interviews with parents and school staff indicated anecdotal gains in attention, EF, emotion-regulation, flexibility, communication, and social skills. Overall, this study provides preliminary support for the feasibility and potential efficacy of the CQ when delivered in schools to children with ASD. En ligne : http://dx.doi.org/10.1007/s10803-020-04723-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=452