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Auteur J. FITZGERALD |
Documents disponibles écrits par cet auteur (2)
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Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells / S. AVAZZADEH in Molecular Autism, 10 (2019)
[article]
Titre : Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells Type de document : Texte imprimé et/ou numérique Auteurs : S. AVAZZADEH, Auteur ; K. MCDONAGH, Auteur ; J. REILLY, Auteur ; Y. WANG, Auteur ; S. D. BOOMKAMP, Auteur ; V. MCINERNEY, Auteur ; J. KRAWCZYK, Auteur ; J. FITZGERALD, Auteur ; N. FEERICK, Auteur ; M. O'SULLIVAN, Auteur ; A. JALALI, Auteur ; E. B. FORMAN, Auteur ; S. A. LYNCH, Auteur ; S. ENNIS, Auteur ; N. COSEMANS, Auteur ; H. PEETERS, Auteur ; P. DOCKERY, Auteur ; T. O'BRIEN, Auteur ; L. R. QUINLAN, Auteur ; L. GALLAGHER, Auteur ; S. SHEN, Auteur Article en page(s) : 52 p. Langues : Anglais (eng) Mots-clés : Autism Calcium signaling Induced pluripotent stem cells NRXN1alpha Neurons Transcriptome Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1alpha (+/-) deletions. Seven control and six NRXN1alpha (+/-) iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca(2+)) imaging was performed using Fluo4-AM, and the properties of Ca(2+) transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1alpha (+/-) neurons. Results: NRXN1alpha (+/-) neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca(2+) transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1alpha (+/-) neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1alpha (+/-) neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca(2+) transients, which may facilitate the development of drug screening assays for the treatment of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0303-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414
in Molecular Autism > 10 (2019) . - 52 p.[article] Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells [Texte imprimé et/ou numérique] / S. AVAZZADEH, Auteur ; K. MCDONAGH, Auteur ; J. REILLY, Auteur ; Y. WANG, Auteur ; S. D. BOOMKAMP, Auteur ; V. MCINERNEY, Auteur ; J. KRAWCZYK, Auteur ; J. FITZGERALD, Auteur ; N. FEERICK, Auteur ; M. O'SULLIVAN, Auteur ; A. JALALI, Auteur ; E. B. FORMAN, Auteur ; S. A. LYNCH, Auteur ; S. ENNIS, Auteur ; N. COSEMANS, Auteur ; H. PEETERS, Auteur ; P. DOCKERY, Auteur ; T. O'BRIEN, Auteur ; L. R. QUINLAN, Auteur ; L. GALLAGHER, Auteur ; S. SHEN, Auteur . - 52 p.
Langues : Anglais (eng)
in Molecular Autism > 10 (2019) . - 52 p.
Mots-clés : Autism Calcium signaling Induced pluripotent stem cells NRXN1alpha Neurons Transcriptome Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a high co-morbidity of epilepsy and associated with hundreds of rare risk factors. NRXN1 deletion is among the commonest rare genetic factors shared by ASD, schizophrenia, intellectual disability, epilepsy, and developmental delay. However, how NRXN1 deletions lead to different clinical symptoms is unknown. Patient-derived cells are essential to investigate the functional consequences of NRXN1 lesions to human neurons in different diseases. Methods: Skin biopsies were donated by five healthy donors and three ASD patients carrying NRXN1alpha (+/-) deletions. Seven control and six NRXN1alpha (+/-) iPSC lines were derived and differentiated into day 100 cortical excitatory neurons using dual SMAD inhibition. Calcium (Ca(2+)) imaging was performed using Fluo4-AM, and the properties of Ca(2+) transients were compared between two groups of neurons. Transcriptome analysis was carried out to undercover molecular pathways associated with NRXN1alpha (+/-) neurons. Results: NRXN1alpha (+/-) neurons were found to display altered calcium dynamics, with significantly increased frequency, duration, and amplitude of Ca(2+) transients. Whole genome RNA sequencing also revealed altered ion transport and transporter activity, with upregulated voltage-gated calcium channels as one of the most significant pathways in NRXN1alpha (+/-) neurons identified by STRING and GSEA analyses. Conclusions: This is the first report to show that human NRXN1alpha (+/-) neurons derived from ASD patients' iPSCs present novel phenotypes of upregulated VGCCs and increased Ca(2+) transients, which may facilitate the development of drug screening assays for the treatment of ASD. En ligne : http://dx.doi.org/10.1186/s13229-019-0303-3 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 Widespread Disrupted White Matter Microstructure in Autism Spectrum Disorders / J. FITZGERALD in Journal of Autism and Developmental Disorders, 49-7 (July 2019)
[article]
Titre : Widespread Disrupted White Matter Microstructure in Autism Spectrum Disorders Type de document : Texte imprimé et/ou numérique Auteurs : J. FITZGERALD, Auteur ; L. GALLAGHER, Auteur ; J. MCGRATH, Auteur Article en page(s) : p.2664-2674 Langues : Anglais (eng) Mots-clés : Autism spectrum disorders Dti Diffusion imaging Fractional anisotropy Structural connectivity Tbss Index. décimale : PER Périodiques Résumé : Autism Spectrum Disorders (ASDs) are characterised by impaired social communication and restricted repetitive behaviours. Researchers posit that these core features may be underpinned by disrupted structural connectivity. A tract based spatial statistical analysis of diffusion MRI data was performed to investigate white matter organisation (an indication of structural connectivity) in a well-defined cohort of 45 ASD and 45 age and IQ matched control participants. Aberrant structural connectivity characterised by reduced fractional anisotropy was observed in several fiber pathways in ASD relative to controls. Disrupted white matter organisation was associated with social deficits and restricted repetitive behaviours in ASD. Abnormal structural connectivity is apparent in ASD and may be linked to the core behavioural features of the disorder. En ligne : http://dx.doi.org/10.1007/s10803-016-2803-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=401
in Journal of Autism and Developmental Disorders > 49-7 (July 2019) . - p.2664-2674[article] Widespread Disrupted White Matter Microstructure in Autism Spectrum Disorders [Texte imprimé et/ou numérique] / J. FITZGERALD, Auteur ; L. GALLAGHER, Auteur ; J. MCGRATH, Auteur . - p.2664-2674.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 49-7 (July 2019) . - p.2664-2674
Mots-clés : Autism spectrum disorders Dti Diffusion imaging Fractional anisotropy Structural connectivity Tbss Index. décimale : PER Périodiques Résumé : Autism Spectrum Disorders (ASDs) are characterised by impaired social communication and restricted repetitive behaviours. Researchers posit that these core features may be underpinned by disrupted structural connectivity. A tract based spatial statistical analysis of diffusion MRI data was performed to investigate white matter organisation (an indication of structural connectivity) in a well-defined cohort of 45 ASD and 45 age and IQ matched control participants. Aberrant structural connectivity characterised by reduced fractional anisotropy was observed in several fiber pathways in ASD relative to controls. Disrupted white matter organisation was associated with social deficits and restricted repetitive behaviours in ASD. Abnormal structural connectivity is apparent in ASD and may be linked to the core behavioural features of the disorder. En ligne : http://dx.doi.org/10.1007/s10803-016-2803-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=401