Bio-collections in autism research / Jamie REILLY in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 34p. Titre : Bio-collections in autism research Type de document : texte imprimé Auteurs : Jamie REILLY, Auteur ; Louise GALLAGHER, Auteur ; June L. CHEN, Auteur ; Geraldine LEADER, Auteur ; Sanbing SHEN, Auteur Article en page(s) : 34p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with diverse clinical manifestations and symptoms. In the last 10 years, there have been significant advances in understanding the genetic basis for ASD, critically supported through the establishment of ASD bio-collections and application in research. Here, we summarise a selection of major ASD bio-collections and their associated findings. Collectively, these include mapping ASD candidate genes, assessing the nature and frequency of gene mutations and their association with ASD clinical subgroups, insights into related molecular pathways such as the synapses, chromatin remodelling, transcription and ASD-related brain regions. We also briefly review emerging studies on the use of induced pluripotent stem cells (iPSCs) to potentially model ASD in culture. These provide deeper insight into ASD progression during development and could generate human cell models for drug screening. Finally, we provide perspectives concerning the utilities of ASD bio-collections and limitations, and highlight considerations in setting up a new bio-collection for ASD research. En ligne : http://dx.doi.org/10.1186/s13229-017-0154-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] Bio-collections in autism research [texte imprimé] / Jamie REILLY, Auteur ; Louise GALLAGHER, Auteur ; June L. CHEN, Auteur ; Geraldine LEADER, Auteur ; Sanbing SHEN, Auteur . - 34p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 34p. Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a group of complex neurodevelopmental disorders with diverse clinical manifestations and symptoms. In the last 10 years, there have been significant advances in understanding the genetic basis for ASD, critically supported through the establishment of ASD bio-collections and application in research. Here, we summarise a selection of major ASD bio-collections and their associated findings. Collectively, these include mapping ASD candidate genes, assessing the nature and frequency of gene mutations and their association with ASD clinical subgroups, insights into related molecular pathways such as the synapses, chromatin remodelling, transcription and ASD-related brain regions. We also briefly review emerging studies on the use of induced pluripotent stem cells (iPSCs) to potentially model ASD in culture. These provide deeper insight into ASD progression during development and could generate human cell models for drug screening. Finally, we provide perspectives concerning the utilities of ASD bio-collections and limitations, and highlight considerations in setting up a new bio-collection for ASD research. En ligne : http://dx.doi.org/10.1186/s13229-017-0154-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions / Jacqueline FITZGERALD in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions Type de document : texte imprimé Auteurs : Jacqueline FITZGERALD, Auteur ; Ciara J. MOLLOY, Auteur ; Thomas DINNEEN, Auteur ; Niamh E. FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Richard O'CONAILL, Auteur ; Maryam AL-SHEHHI, Auteur ; Richard REILLY, Auteur ; Sally Ann LYNCH, Auteur ; Eleisa A. HERON, Auteur ; Clare KELLY, Auteur ; Sanbing SHEN, Auteur ; Louise GALLAGHER, Auteur Langues : Anglais (eng) Mots-clés : Humans  Female  Male  Magnetic Resonance Imaging  Adult  Young Adult  Calcium-Binding Proteins/genetics  Diffusion Tensor Imaging  Brain/diagnostic imaging/physiopathology  Neural Cell Adhesion Molecules/genetics  Adolescent  Cell Adhesion Molecules, Neuronal/genetics  Cognition/physiology  Neuropsychological Tests  Gene Deletion  Neural Pathways/diagnostic imaging/physiopathology  Executive Function/physiology  Cognition  Copy number variant  NRXN1 deletion  Neuroimaging  the study was obtained from St. James’s Hospital/Tallaght University Hospital  Research Ethics Committee (REC reference: 2015/03/01). Participants over 18 years  provided written consent and parental written consent was provided for those  under 18 years. Consent for publication: All authors who contributed to the  article have approved the submitted version. Competing interests: The authors  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: NRXN1 deletion (NRXN1 del) is a rare copy number variant associated with several neurodevelopmental, neuropsychiatric, and cognitive outcomes. The NRXN1 gene encodes for a pre-synaptic cell adhesion molecule that is important for synapse formation, regulation and neurotransmission. We used a gene-first approach to investigate neurocognitive and brain phenotypes in NRXN1 del carriers. METHODS: Forty-two participants (21 NRXN1 del carriers and 21 neurotypical age and sex-matched comparisons) completed IQ assessments, and a neurocognitive battery, including, executive function, attention, and social cognition tasks. Magnetic resonance imaging (MRI) data, including T1-weighted anatomical scans, resting state functional MRI and diffusion tensor imaging, were acquired in 36 participants (17 NRXN1 del carriers and 19 comparisons). RESULTS: NRXN1 del carriers had lower mean IQ and poorer spatial working memory performance compared to comparisons (p ≤ 0.05). Neuroimaging results revealed group differences in visual and ventral attention resting state networks (p < 0.05). Network-based statistical analysis showed a significant effect of group status for 28/115 connections, with poorer segregation between visual and default networks in NRXN1 del carriers relative to comparisons. No differences in brain structural volume or cortical thickness, or diffusion measures of white matter structural architecture were observed between groups. CONCLUSIONS: This exploratory study provides evidence for neurocognitive impacts and brain functional differences related to underlying synaptic mechanisms. Brain functional differences in NRXN1 del carriers may support altered excitation/inhibition dynamics within the brain. Gene-first approaches may establish brain-based translational markers to identify neurobiologically informed subgroups within neurodevelopmental and neuropsychiatric conditions, and ultimately transdiagnostic therapeutic strategies. En ligne : https://dx.doi.org/10.1186/s11689-025-09625-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] Evidence of neurocognitive and resting state functional connectivity differences in carriers of NRXN1 deletions [texte imprimé] / Jacqueline FITZGERALD, Auteur ; Ciara J. MOLLOY, Auteur ; Thomas DINNEEN, Auteur ; Niamh E. FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Richard O'CONAILL, Auteur ; Maryam AL-SHEHHI, Auteur ; Richard REILLY, Auteur ; Sally Ann LYNCH, Auteur ; Eleisa A. HERON, Auteur ; Clare KELLY, Auteur ; Sanbing SHEN, Auteur ; Louise GALLAGHER, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Humans  Female  Male  Magnetic Resonance Imaging  Adult  Young Adult  Calcium-Binding Proteins/genetics  Diffusion Tensor Imaging  Brain/diagnostic imaging/physiopathology  Neural Cell Adhesion Molecules/genetics  Adolescent  Cell Adhesion Molecules, Neuronal/genetics  Cognition/physiology  Neuropsychological Tests  Gene Deletion  Neural Pathways/diagnostic imaging/physiopathology  Executive Function/physiology  Cognition  Copy number variant  NRXN1 deletion  Neuroimaging  the study was obtained from St. James’s Hospital/Tallaght University Hospital  Research Ethics Committee (REC reference: 2015/03/01). Participants over 18 years  provided written consent and parental written consent was provided for those  under 18 years. Consent for publication: All authors who contributed to the  article have approved the submitted version. Competing interests: The authors  declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: NRXN1 deletion (NRXN1 del) is a rare copy number variant associated with several neurodevelopmental, neuropsychiatric, and cognitive outcomes. The NRXN1 gene encodes for a pre-synaptic cell adhesion molecule that is important for synapse formation, regulation and neurotransmission. We used a gene-first approach to investigate neurocognitive and brain phenotypes in NRXN1 del carriers. METHODS: Forty-two participants (21 NRXN1 del carriers and 21 neurotypical age and sex-matched comparisons) completed IQ assessments, and a neurocognitive battery, including, executive function, attention, and social cognition tasks. Magnetic resonance imaging (MRI) data, including T1-weighted anatomical scans, resting state functional MRI and diffusion tensor imaging, were acquired in 36 participants (17 NRXN1 del carriers and 19 comparisons). RESULTS: NRXN1 del carriers had lower mean IQ and poorer spatial working memory performance compared to comparisons (p ≤ 0.05). Neuroimaging results revealed group differences in visual and ventral attention resting state networks (p < 0.05). Network-based statistical analysis showed a significant effect of group status for 28/115 connections, with poorer segregation between visual and default networks in NRXN1 del carriers relative to comparisons. No differences in brain structural volume or cortical thickness, or diffusion measures of white matter structural architecture were observed between groups. CONCLUSIONS: This exploratory study provides evidence for neurocognitive impacts and brain functional differences related to underlying synaptic mechanisms. Brain functional differences in NRXN1 del carriers may support altered excitation/inhibition dynamics within the brain. Gene-first approaches may establish brain-based translational markers to identify neurobiologically informed subgroups within neurodevelopmental and neuropsychiatric conditions, and ultimately transdiagnostic therapeutic strategies. En ligne : https://dx.doi.org/10.1186/s11689-025-09625-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells / Sahar AVAZZADEH in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 52 p. Titre : Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells Type de document : texte imprimé Auteurs : Sahar AVAZZADEH, Auteur ; Katya MCDONAGH, Auteur ; Jamie REILLY, Auteur ; Yao WANG, Auteur ; Stephanie D. BOOMKAMP, Auteur ; Veronica MCINERNEY, Auteur ; Janusz KRAWCZYK, Auteur ; Jacqueline FITZGERALD, Auteur ; Niamh FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Amirhossein JALALI, Auteur ; Eva B. FORMAN, Auteur ; Sally A. LYNCH, Auteur ; Sean ENNIS, Auteur ; Nele COSEMANS, Auteur ; Hilde PEETERS, Auteur ; Peter DOCKERY, Auteur ; Timothy O'BRIEN, Auteur ; Leo R. QUINLAN, Auteur ; Louise GALLAGHER, Auteur ; Sanbing 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 [article] Increased Ca(2+) signaling in NRXN1alpha (+/-) neurons derived from ASD induced pluripotent stem cells [texte imprimé] / Sahar AVAZZADEH, Auteur ; Katya MCDONAGH, Auteur ; Jamie REILLY, Auteur ; Yao WANG, Auteur ; Stephanie D. BOOMKAMP, Auteur ; Veronica MCINERNEY, Auteur ; Janusz KRAWCZYK, Auteur ; Jacqueline FITZGERALD, Auteur ; Niamh FEERICK, Auteur ; Matthew O'SULLIVAN, Auteur ; Amirhossein JALALI, Auteur ; Eva B. FORMAN, Auteur ; Sally A. LYNCH, Auteur ; Sean ENNIS, Auteur ; Nele COSEMANS, Auteur ; Hilde PEETERS, Auteur ; Peter DOCKERY, Auteur ; Timothy O'BRIEN, Auteur ; Leo R. QUINLAN, Auteur ; Louise GALLAGHER, Auteur ; Sanbing 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

Molecular Pathways in Autistic Spectrum Disorders / Louise GALLAGHER in Key Issues in Mental Health, 180 (2015)

Public ISBD [article]  inKey Issues in Mental Health > 180 (2015) . - p.97-112 Titre : Molecular Pathways in Autistic Spectrum Disorders Type de document : texte imprimé Auteurs : Louise GALLAGHER, Auteur ; Sanbing SHEN, Auteur ; Richard ANNEY, Auteur Article en page(s) : p.97-112 Langues : Anglais (eng) Index. décimale : AUT-B AUT-B - L'Autisme - Ouvrages généraux et scientifiques Résumé : Major advances in neuroscience have highlighted previously elusive molecular pathways for autistic spectrum disorders (ASD) which are essential to the identification of molecular targets for drug discovery. The evidence of the heritability of ASD is now well established, and the last decade brought an exponential rate of discovery in ASD genetics. In particular rare chromosomal structural rearrangements and rare sequence variants have been implicated, with common genetic variation conferring a modest risk. Rare genetic mutations of major effect offer direct targets for the study of underlying molecular mechanisms. Systems biology approaches such as data mining of large genetic data sets in ASD are also used to identify related functional pathways. A greater understanding of the neural mechanisms underpinning ASD is required to determine disrupted developmental processes and how and when pharmacological and behavioural interventions are best initiated. Identification of the disease mechanisms associated with monogenetic neurodevelopmental disorders such as Rett syndrome and fragile X syndrome have led to new molecular targets and potential treatments which have provided optimism for researchers and the ASD community. Taken together, rare and common genetic variations in ASD implicate critical pathways involving chromatin remodelling, synaptogenesis, synapse specialization and intracellular signalling mechanisms. The following chapter will synthesize evidence from a range of sources to illustrate the molecular pathways that appear to be most implicated in ASD, providing potential targets for new drug exploitation. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=271 [article] Molecular Pathways in Autistic Spectrum Disorders [texte imprimé] / Louise GALLAGHER, Auteur ; Sanbing SHEN, Auteur ; Richard ANNEY, Auteur . - p.97-112. Langues : Anglais (eng) in Key Issues in Mental Health > 180 (2015) . - p.97-112 Index. décimale : AUT-B AUT-B - L'Autisme - Ouvrages généraux et scientifiques Résumé : Major advances in neuroscience have highlighted previously elusive molecular pathways for autistic spectrum disorders (ASD) which are essential to the identification of molecular targets for drug discovery. The evidence of the heritability of ASD is now well established, and the last decade brought an exponential rate of discovery in ASD genetics. In particular rare chromosomal structural rearrangements and rare sequence variants have been implicated, with common genetic variation conferring a modest risk. Rare genetic mutations of major effect offer direct targets for the study of underlying molecular mechanisms. Systems biology approaches such as data mining of large genetic data sets in ASD are also used to identify related functional pathways. A greater understanding of the neural mechanisms underpinning ASD is required to determine disrupted developmental processes and how and when pharmacological and behavioural interventions are best initiated. Identification of the disease mechanisms associated with monogenetic neurodevelopmental disorders such as Rett syndrome and fragile X syndrome have led to new molecular targets and potential treatments which have provided optimism for researchers and the ASD community. Taken together, rare and common genetic variations in ASD implicate critical pathways involving chromatin remodelling, synaptogenesis, synapse specialization and intracellular signalling mechanisms. The following chapter will synthesize evidence from a range of sources to illustrate the molecular pathways that appear to be most implicated in ASD, providing potential targets for new drug exploitation. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=271

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