38 recherche sur le mot-clé 'Angelman syndrome'

Evaluation of electroencephalography biomarkers for Angelman syndrome during overnight sleep / Yuval LEVIN in Autism Research, 15-6 (June 2022)  

Public ISBD [article]  inAutism Research > 15-6 (June 2022) . - p.1031-1042 Titre : Evaluation of electroencephalography biomarkers for Angelman syndrome during overnight sleep Type de document : texte imprimé Auteurs : Yuval LEVIN, Auteur ; Nishitha S. HOSAMANE, Auteur ; Taylor E. MCNAIR, Auteur ; Shrujana S. KUNNAM, Auteur ; Benjamin D. PHILPOT, Auteur ; Zheng FAN, Auteur ; Michael S. SIDOROV, Auteur Article en page(s) : p.1031-1042 Langues : Anglais (eng) Mots-clés : Angelman Syndrome/complications/diagnosis/genetics  Autism Spectrum Disorder  Biomarkers  Electroencephalography  Humans  Retrospective Studies  Sleep/physiology  Angelman syndrome  Eeg  biomarker  delta  sleep  spindle  Medpace, Inc. for EEG analysis. Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss-of-function mutations in the maternal copy of the UBE3A gene. AS is characterized by intellectual disability, impaired speech and motor skills, epilepsy, and sleep disruptions. Multiple treatment strategies to re-express functional neuronal UBE3A from the dormant paternal allele were successful in rodent models of AS and have now moved to early phase clinical trials in children. Developing reliable and objective AS biomarkers is essential to guide the design and execution of current and future clinical trials. Our prior work quantified short daytime electroencephalograms (EEGs) to define promising biomarkers for AS. Here, we asked whether overnight sleep is better suited to detect AS EEG biomarkers. We retrospectively analyzed EEGs from 12 overnight sleep studies from individuals with AS with age and sex-matched Down syndrome and neurotypical controls, focusing on low frequency (2-4 Hz) delta rhythms and sleep spindles. Delta EEG rhythms were increased in individuals with AS during all stages of overnight sleep, but overnight sleep did not provide additional benefit over wake in the ability to detect increased delta. Abnormal sleep spindles were not reliably detected in EEGs from individuals with AS during overnight sleep, suggesting that delta rhythms represent a more reliable biomarker. Overall, we conclude that periods of wakefulness are sufficient, and perhaps ideal, to quantify delta EEG rhythms for use as AS biomarkers. LAY SUMMARY: Electroencephalography (EEG) is a safe and reliable way of measuring abnormal brain activity in Angelman syndrome. We found that low-frequency "delta" EEG rhythms are increased in individuals with Angelman syndrome during all stages of overnight sleep. Delta rhythms can be used as a tool to measure improvement in future clinical trials. En ligne : http://dx.doi.org/10.1002/aur.2709 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476 [article] Evaluation of electroencephalography biomarkers for Angelman syndrome during overnight sleep [texte imprimé] / Yuval LEVIN, Auteur ; Nishitha S. HOSAMANE, Auteur ; Taylor E. MCNAIR, Auteur ; Shrujana S. KUNNAM, Auteur ; Benjamin D. PHILPOT, Auteur ; Zheng FAN, Auteur ; Michael S. SIDOROV, Auteur . - p.1031-1042. Langues : Anglais (eng) in Autism Research > 15-6 (June 2022) . - p.1031-1042 Mots-clés : Angelman Syndrome/complications/diagnosis/genetics  Autism Spectrum Disorder  Biomarkers  Electroencephalography  Humans  Retrospective Studies  Sleep/physiology  Angelman syndrome  Eeg  biomarker  delta  sleep  spindle  Medpace, Inc. for EEG analysis. Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss-of-function mutations in the maternal copy of the UBE3A gene. AS is characterized by intellectual disability, impaired speech and motor skills, epilepsy, and sleep disruptions. Multiple treatment strategies to re-express functional neuronal UBE3A from the dormant paternal allele were successful in rodent models of AS and have now moved to early phase clinical trials in children. Developing reliable and objective AS biomarkers is essential to guide the design and execution of current and future clinical trials. Our prior work quantified short daytime electroencephalograms (EEGs) to define promising biomarkers for AS. Here, we asked whether overnight sleep is better suited to detect AS EEG biomarkers. We retrospectively analyzed EEGs from 12 overnight sleep studies from individuals with AS with age and sex-matched Down syndrome and neurotypical controls, focusing on low frequency (2-4 Hz) delta rhythms and sleep spindles. Delta EEG rhythms were increased in individuals with AS during all stages of overnight sleep, but overnight sleep did not provide additional benefit over wake in the ability to detect increased delta. Abnormal sleep spindles were not reliably detected in EEGs from individuals with AS during overnight sleep, suggesting that delta rhythms represent a more reliable biomarker. Overall, we conclude that periods of wakefulness are sufficient, and perhaps ideal, to quantify delta EEG rhythms for use as AS biomarkers. LAY SUMMARY: Electroencephalography (EEG) is a safe and reliable way of measuring abnormal brain activity in Angelman syndrome. We found that low-frequency "delta" EEG rhythms are increased in individuals with Angelman syndrome during all stages of overnight sleep. Delta rhythms can be used as a tool to measure improvement in future clinical trials. En ligne : http://dx.doi.org/10.1002/aur.2709 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=476

Gait as a quantitative translational outcome measure in Angelman syndrome / Stela P. PETKOVA in Autism Research, 15-5 (May 2022)  

Public ISBD [article]  inAutism Research > 15-5 (May 2022) . - p.821-833 Titre : Gait as a quantitative translational outcome measure in Angelman syndrome Type de document : texte imprimé Auteurs : Stela P. PETKOVA, Auteur ; Anna ADHIKARI, Auteur ; Elizabeth L. BERG, Auteur ; Timothy A. FENTON, Auteur ; Jessica DUIS, Auteur ; Jill L. SILVERMAN, Auteur Article en page(s) : p.821-833 Langues : Anglais (eng) Mots-clés : Angelman Syndrome/genetics  Animals  Autism Spectrum Disorder  Disease Models, Animal  Gait/physiology  Humans  Mice  Movement Disorders  Muscle Hypotonia  Outcome Assessment, Health Care  Angelman syndrome  animal models  autism  behavior  gait  genetics  longitudinal  motor  mouse models  neurodevelopment Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS) is a genetic neurodevelopmental disorder characterized by developmental delay, lack of speech, seizures, intellectual disability, hypotonia, and motor coordination deficits. Motor abilities are an important outcome measure in AS as they comprise a broad repertoire of metrics including ataxia, hypotonia, delayed ambulation, crouched gait, and poor posture, and motor dysfunction affects nearly every individual with AS. Guided by collaborative work with AS clinicians studying gait, the goal of this study was to perform an in-depth gait analysis using the automated treadmill assay, DigiGait. Our hypothesis is that gait presents a strong opportunity for a reliable, quantitative, and translational metric that can serve to evaluate novel pharmacological, dietary, and genetic therapies. In this study, we used an automated gait analysis system, in addition to standard motor behavioral assays, to evaluate components of motor, exploration, coordination, balance, and gait impairments across the lifespan in an AS mouse model. Our study demonstrated marked global motoric deficits in AS mice, corroborating previous reports. Uniquely, this is the first report of nuanced aberrations in quantitative spatial and temporal components of gait in AS mice compared to sex- and age-matched wildtype littermates followed longitudinally using metrics that are analogous in AS individuals. Our findings contribute evidence toward the use of nuanced motor outcomes (i.e., gait) as valuable and translationally powerful metrics for therapeutic development for AS, as well as other genetic neurodevelopmental syndromes. LAY SUMMARY: Movement disorders affect nearly every individual with Angelman Syndrome (AS). The most common motor problems include spasticity, ataxia of gait (observed in the majority of ambulatory individuals), tremor, and muscle weakness. This report focused on quantifying various spatial and temporal aspects of gait as a reliable, translatable outcome measure in a preclinical AS model longitudinally across development. By increasing the number of translational, reliable, functional outcome measures in our wheelhouse, we will create more opportunities for identifying and advancing successful medical interventions. En ligne : http://dx.doi.org/10.1002/aur.2697 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=473 [article] Gait as a quantitative translational outcome measure in Angelman syndrome [texte imprimé] / Stela P. PETKOVA, Auteur ; Anna ADHIKARI, Auteur ; Elizabeth L. BERG, Auteur ; Timothy A. FENTON, Auteur ; Jessica DUIS, Auteur ; Jill L. SILVERMAN, Auteur . - p.821-833. Langues : Anglais (eng) in Autism Research > 15-5 (May 2022) . - p.821-833 Mots-clés : Angelman Syndrome/genetics  Animals  Autism Spectrum Disorder  Disease Models, Animal  Gait/physiology  Humans  Mice  Movement Disorders  Muscle Hypotonia  Outcome Assessment, Health Care  Angelman syndrome  animal models  autism  behavior  gait  genetics  longitudinal  motor  mouse models  neurodevelopment Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS) is a genetic neurodevelopmental disorder characterized by developmental delay, lack of speech, seizures, intellectual disability, hypotonia, and motor coordination deficits. Motor abilities are an important outcome measure in AS as they comprise a broad repertoire of metrics including ataxia, hypotonia, delayed ambulation, crouched gait, and poor posture, and motor dysfunction affects nearly every individual with AS. Guided by collaborative work with AS clinicians studying gait, the goal of this study was to perform an in-depth gait analysis using the automated treadmill assay, DigiGait. Our hypothesis is that gait presents a strong opportunity for a reliable, quantitative, and translational metric that can serve to evaluate novel pharmacological, dietary, and genetic therapies. In this study, we used an automated gait analysis system, in addition to standard motor behavioral assays, to evaluate components of motor, exploration, coordination, balance, and gait impairments across the lifespan in an AS mouse model. Our study demonstrated marked global motoric deficits in AS mice, corroborating previous reports. Uniquely, this is the first report of nuanced aberrations in quantitative spatial and temporal components of gait in AS mice compared to sex- and age-matched wildtype littermates followed longitudinally using metrics that are analogous in AS individuals. Our findings contribute evidence toward the use of nuanced motor outcomes (i.e., gait) as valuable and translationally powerful metrics for therapeutic development for AS, as well as other genetic neurodevelopmental syndromes. LAY SUMMARY: Movement disorders affect nearly every individual with Angelman Syndrome (AS). The most common motor problems include spasticity, ataxia of gait (observed in the majority of ambulatory individuals), tremor, and muscle weakness. This report focused on quantifying various spatial and temporal aspects of gait as a reliable, translatable outcome measure in a preclinical AS model longitudinally across development. By increasing the number of translational, reliable, functional outcome measures in our wheelhouse, we will create more opportunities for identifying and advancing successful medical interventions. En ligne : http://dx.doi.org/10.1002/aur.2697 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=473

CIM6P/IGF-2 Receptor Ligands Reverse Deficits in Angelman Syndrome Model Mice / Emmanuel CRUZ in Autism Research, 14-1 (January 2021)  

Public ISBD [article]  inAutism Research > 14-1 (January 2021) . - p.29-45 Titre : CIM6P/IGF-2 Receptor Ligands Reverse Deficits in Angelman Syndrome Model Mice Type de document : texte imprimé Auteurs : Emmanuel CRUZ, Auteur ; Giannina DESCALZI, Auteur ; Adam STEINMETZ, Auteur ; Helen E. SCHARFMAN, Auteur ; Aaron KATZMAN, Auteur ; Cristina M. ALBERINI, Auteur Article en page(s) : p.29-45 Langues : Anglais (eng) Mots-clés : Angelman syndrome  Ube3a  audiogenic seizure  cation-independent mannose-6-phosphate receptor  insulin-like growth factor 2  insulin-like growth factor 2 receptor  mannose-6-phosphate  memory  motor response  mouse model Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS), a genetic disorder that primarily affects the nervous system, is characterized by delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy). No existing therapies are capable of comprehensively treating the deficits in AS; hence, there is an urgent need to identify new treatments. Here we show that insulin-like growth factor 2 (IGF-2) and mannose-6-phosphate (M6P), ligands of two independent binding sites of the cation-independent M6P/IGF-2 receptor (CIM6P/IGF-2R), reverse most major deficits of AS modeled in mice. Subcutaneous injection of IGF-2 or M6P in mice modeling AS restored cognitive impairments as assessed by measurements of contextual and recognition memories, motor deficits assessed by rotarod and hindlimb clasping, and working memory/flexibility measured by Y-maze. IGF-2 also corrected deficits in marble burying and significantly attenuated acoustically induced seizures. An observational battery of tests confirmed that neither ligand changed basic functions including physical characteristics, general behavioral responses, and sensory reflexes, indicating that they are relatively safe. Our data provide strong preclinical evidence that targeting CIM6P/IGF-2R is a promising approach for developing novel therapeutics for AS. LAY SUMMARY: There is no effective treatment for the neurodevelopmental disorder Angelman syndrome (AS). Using a validated AS mouse model, the Ube3a(m-/p+) , in this study we show that systemic administration of ligands of the cation independent mannose-6-phosphate receptor, also known as insulin-like growth factor 2 receptor (CIM6P/IGF-2R) reverses cognitive impairment, motor deficits, as well as seizures associated with AS. Thus, ligands that activate the CIM6P/IGF-2R may represent novel, potential therapeutic targets for AS. En ligne : http://dx.doi.org/10.1002/aur.2418 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=441 [article] CIM6P/IGF-2 Receptor Ligands Reverse Deficits in Angelman Syndrome Model Mice [texte imprimé] / Emmanuel CRUZ, Auteur ; Giannina DESCALZI, Auteur ; Adam STEINMETZ, Auteur ; Helen E. SCHARFMAN, Auteur ; Aaron KATZMAN, Auteur ; Cristina M. ALBERINI, Auteur . - p.29-45. Langues : Anglais (eng) in Autism Research > 14-1 (January 2021) . - p.29-45 Mots-clés : Angelman syndrome  Ube3a  audiogenic seizure  cation-independent mannose-6-phosphate receptor  insulin-like growth factor 2  insulin-like growth factor 2 receptor  mannose-6-phosphate  memory  motor response  mouse model Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS), a genetic disorder that primarily affects the nervous system, is characterized by delayed development, intellectual disability, severe speech impairment, and problems with movement and balance (ataxia). Most affected children also have recurrent seizures (epilepsy). No existing therapies are capable of comprehensively treating the deficits in AS; hence, there is an urgent need to identify new treatments. Here we show that insulin-like growth factor 2 (IGF-2) and mannose-6-phosphate (M6P), ligands of two independent binding sites of the cation-independent M6P/IGF-2 receptor (CIM6P/IGF-2R), reverse most major deficits of AS modeled in mice. Subcutaneous injection of IGF-2 or M6P in mice modeling AS restored cognitive impairments as assessed by measurements of contextual and recognition memories, motor deficits assessed by rotarod and hindlimb clasping, and working memory/flexibility measured by Y-maze. IGF-2 also corrected deficits in marble burying and significantly attenuated acoustically induced seizures. An observational battery of tests confirmed that neither ligand changed basic functions including physical characteristics, general behavioral responses, and sensory reflexes, indicating that they are relatively safe. Our data provide strong preclinical evidence that targeting CIM6P/IGF-2R is a promising approach for developing novel therapeutics for AS. LAY SUMMARY: There is no effective treatment for the neurodevelopmental disorder Angelman syndrome (AS). Using a validated AS mouse model, the Ube3a(m-/p+) , in this study we show that systemic administration of ligands of the cation independent mannose-6-phosphate receptor, also known as insulin-like growth factor 2 receptor (CIM6P/IGF-2R) reverses cognitive impairment, motor deficits, as well as seizures associated with AS. Thus, ligands that activate the CIM6P/IGF-2R may represent novel, potential therapeutic targets for AS. En ligne : http://dx.doi.org/10.1002/aur.2418 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=441

Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion / Andie DODGE in Autism Research, 13-3 (March 2020)  

Public ISBD [article]  inAutism Research > 13-3 (March 2020) . - p.397-409 Titre : Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion Type de document : texte imprimé Auteurs : Andie DODGE, Auteur ; Melinda M. PETERS, Auteur ; Hayden E. GREENE, Auteur ; Clifton DIETRICK, Auteur ; Robert BOTELHO, Auteur ; Diana CHUNG, Auteur ; Jonathan WILLMAN, Auteur ; Austin W NENNINGER, Auteur ; Stephanie CIARLONE, Auteur ; Siddharth G. KAMATH, Auteur ; Pavel HOUDEK, Auteur ; Alena SUMOVA, Auteur ; Anne E. ANDERSON, Auteur ; Scott V. DINDOT, Auteur ; Elizabeth L. BERG, Auteur ; Henriette O'GEEN, Auteur ; David J. SEGAL, Auteur ; Jill L. SILVERMAN, Auteur ; Edwin J. WEEBER, Auteur ; Kevin R. NASH, Auteur Article en page(s) : p.397-409 Langues : Anglais (eng) Mots-clés : Angelman syndrome  E6ap  Ube3a  cognitive deficits  rat model Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397-409. (c) 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. En ligne : http://dx.doi.org/10.1002/aur.2267 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421 [article] Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion [texte imprimé] / Andie DODGE, Auteur ; Melinda M. PETERS, Auteur ; Hayden E. GREENE, Auteur ; Clifton DIETRICK, Auteur ; Robert BOTELHO, Auteur ; Diana CHUNG, Auteur ; Jonathan WILLMAN, Auteur ; Austin W NENNINGER, Auteur ; Stephanie CIARLONE, Auteur ; Siddharth G. KAMATH, Auteur ; Pavel HOUDEK, Auteur ; Alena SUMOVA, Auteur ; Anne E. ANDERSON, Auteur ; Scott V. DINDOT, Auteur ; Elizabeth L. BERG, Auteur ; Henriette O'GEEN, Auteur ; David J. SEGAL, Auteur ; Jill L. SILVERMAN, Auteur ; Edwin J. WEEBER, Auteur ; Kevin R. NASH, Auteur . - p.397-409. Langues : Anglais (eng) in Autism Research > 13-3 (March 2020) . - p.397-409 Mots-clés : Angelman syndrome  E6ap  Ube3a  cognitive deficits  rat model Index. décimale : PER Périodiques Résumé : Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. Elucidating the mechanistic action of E6AP would enhance our understanding of AS and drive current research into new avenues that could lead to novel therapeutic approaches that target E6AP's various functions. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat phenotypically mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. Autism Res 2020, 13: 397-409. (c) 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, difficulty speaking, and ataxia. The gene responsible for AS was identified as UBE3A, yet very little is known about its function in vivo or how the lack of this protein in neurons may contribute to the AS phenotype. To facilitate the study of AS, we have generated a novel rat model in which we deleted the rat Ube3a gene using CRISPR. The AS rat mirrors human AS with loss of Ube3a expression in the brain and deficits in motor coordination as well as learning and memory. This model offers a new avenue for the study of AS. En ligne : http://dx.doi.org/10.1002/aur.2267 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=421

(1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome / Pooja Kri GUPTA in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 31p. Titre : (1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome Type de document : texte imprimé Auteurs : Pooja Kri GUPTA, Auteur ; Sharon BARAK, Auteur ; Yonatan FEUERMANN, Auteur ; Gil GOOBES, Auteur ; Hanoch KAPHZAN, Auteur Article en page(s) : 31p. Langues : Anglais (eng) Mots-clés : Animals  Angelman Syndrome/metabolism/genetics  Metabolomics  Disease Models, Animal  Brain/metabolism/diagnostic imaging  Mice  Proton Magnetic Resonance Spectroscopy  Metabolome  Ubiquitin-Protein Ligases/metabolism/genetics  Female  Acetate  Angelman syndrome  Developmental disorders  Glycolysis  Lactate  Metabolite  Mitochondria  Pyruvate metabolism  Reactive oxygen species  Succinate Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. METHODS: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. RESULTS: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. LIMITATIONS: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. CONCLUSIONS: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development. En ligne : https://dx.doi.org/10.1186/s13229-024-00608-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538 [article] (1)H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome [texte imprimé] / Pooja Kri GUPTA, Auteur ; Sharon BARAK, Auteur ; Yonatan FEUERMANN, Auteur ; Gil GOOBES, Auteur ; Hanoch KAPHZAN, Auteur . - 31p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 31p. Mots-clés : Animals  Angelman Syndrome/metabolism/genetics  Metabolomics  Disease Models, Animal  Brain/metabolism/diagnostic imaging  Mice  Proton Magnetic Resonance Spectroscopy  Metabolome  Ubiquitin-Protein Ligases/metabolism/genetics  Female  Acetate  Angelman syndrome  Developmental disorders  Glycolysis  Lactate  Metabolite  Mitochondria  Pyruvate metabolism  Reactive oxygen species  Succinate Index. décimale : PER Périodiques Résumé : BACKGROUND: Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function of the ubiquitin ligase E3A (UBE3A) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial function in AS is altered during mid to late embryonic brain development leading to increased oxidative stress and enhanced apoptosis of neural precursor cells. However, the overall alterations of metabolic processes are still unknown. Hence, as a follow-up, we aim to investigate the metabolic profiles of wild-type (WT) and AS littermates and to identify which metabolic processes are aberrant in the brain of AS model mice during embryonic development. METHODS: We collected brain tissue samples from mice embryos at E16.5 and performed metabolomic analyses using proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. Multivariate and Univariate analyses were performed to determine the significantly altered metabolites in AS mice. Pathways associated with the altered metabolites were identified using metabolite set enrichment analysis. RESULTS: Our analysis showed that overall, the metabolomic fingerprint of AS embryonic brains differed from those of their WT littermates. Moreover, we revealed a significant elevation of distinct metabolites, such as acetate, lactate, and succinate in the AS samples compared to the WT samples. The elevated metabolites were significantly associated with the pyruvate metabolism and glycolytic pathways. LIMITATIONS: Only 14 metabolites were successfully identified and investigated in the present study. The effect of unidentified metabolites and their unresolved peaks was not determined. Additionally, we conducted the metabolomic study on whole brain tissue samples. Employing high-resolution NMR studies on different brain regions could further expand our knowledge regarding metabolic alterations in the AS brain. Furthermore, increasing the sample size could reveal the involvement of more significantly altered metabolites in the pathophysiology of the AS brain. CONCLUSIONS: Ube3a loss of function alters bioenergy-related metabolism in the AS brain during embryonic development. Furthermore, these neurochemical changes could be linked to the mitochondrial reactive oxygen species and oxidative stress that occurs during the AS embryonic development. En ligne : https://dx.doi.org/10.1186/s13229-024-00608-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=538

Abnormal coherence and sleep composition in children with Angelman syndrome: a retrospective EEG study / Hanna DEN BAKKER in Molecular Autism, 9 (2018)  

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Acute administration of lovastatin had no pronounced effect on motor abilities, motor coordination, gait nor simple cognition in a mouse model of Angelman syndrome / Timothy A. FENTON in Journal of Neurodevelopmental Disorders, 17 (2025)  

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Cortical and subcortical morphological alteration in Angelman syndrome / Xiaonan DU in Journal of Neurodevelopmental Disorders, 15 (2023)  

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Development of the Angelman syndrome video assessment: quantifying meaningful change / Kriszha A. SHEEHY in Journal of Neurodevelopmental Disorders, 17 (2025)  

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Enabling endpoint development for interventional clinical trials in individuals with Angelman syndrome: a prospective, longitudinal, observational clinical study (FREESIAS) / Jorrit TJEERTES in Journal of Neurodevelopmental Disorders, 15 (2023)  

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