16 recherche sur le mot-clé 'interest.'

Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort / Ting MEI in Molecular Autism, 15 (2024)  

Public ISBD [article]  inMolecular Autism > 15 (2024) . - 3p. Titre : Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort Type de document : texte imprimé Auteurs : Ting MEI, Auteur ; Alberto LLERA, Auteur ; Natalie J. FORDE, Auteur ; Daan VAN ROOIJ, Auteur ; Dorothea L. FLORIS, Auteur ; Christian F. BECKMANN, Auteur ; Jan K. BUITELAAR, Auteur Article en page(s) : 3p. Langues : Anglais (eng) Mots-clés : Humans  Gray Matter/diagnostic imaging  Autistic Disorder/diagnostic imaging  Autism Spectrum Disorder/diagnostic imaging  Retrospective Studies  Magnetic Resonance Imaging/methods  Brain/diagnostic imaging  Autism  Gray matter volume covariation  Replication  advisory board member of, and a speaker for Janssen Cilag BV, Eli Lilly, Shire,  Lundbeck, Roche, and Servier. He is not an employee of any of these companies,  and not a stock shareholder of any of these companies. He has no other financial  or material support, including expert testimony, patents or royalties. The  present work is unrelated to the above grants and relationships. The other  authors report no biomedical financial interests or potential conflicts of  interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robustness of our previous findings, we aimed to replicate our results using data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) autism working group. METHODS: We studied 781 autistic and 927 non-autistic individuals (6-30 years, IQ?? 50), across 37 sites. Voxel-based morphometry was used to quantify GM volume as before. Subsequently, we used spatial maps of the two autism-related independent components (ICs) previously identified in the LEAP sample as templates for regression analyses to separately estimate the ENIGMA-participant loadings to each of these two ICs. Between-group differences in participants' loadings on each component were examined, and we additionally investigated the relation between participant loadings and autistic behaviors within the autism group. RESULTS: The two components of interest, previously identified in the LEAP dataset, showed significant between-group differences upon regressions into the ENIGMA cohort. The associated brain patterns were consistent with those found in the initial identification study. The first IC was primarily associated with increased volumes of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and caudate in the autism group relative to the control group (? = 0.129, p = 0.013). The second IC was related to increased volumes of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to non-autistic individuals (? = 0.116, p = 0.024). However, when accounting for the site-by-group interaction effect, no significant main effect of the group can be identified (p > 0.590). We did not find significant univariate association between the brain measures and behavior in autism (p > 0.085). LIMITATIONS: The distributions of age, IQ, and sex between LEAP and ENIGMA are statistically different from each other. Owing to limited access to the behavioral data of the autism group, we were unable to further our understanding of the neural basis of behavioral dimensions of the sample. CONCLUSIONS: The current study is unable to fully replicate the autism-related brain patterns from LEAP in the ENIGMA cohort. The diverse group effects across ENIGMA sites demonstrate the challenges of generalizing the average findings of the GM covariation patterns to a large-scale cohort integrated retrospectively from multiple studies. Further analyses need to be conducted to gain additional insights into the generalizability of these two GM covariation patterns. En ligne : https://dx.doi.org/10.1186/s13229-024-00583-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537 [article] Gray matter covariations in autism: out-of-sample replication using the ENIGMA autism cohort [texte imprimé] / Ting MEI, Auteur ; Alberto LLERA, Auteur ; Natalie J. FORDE, Auteur ; Daan VAN ROOIJ, Auteur ; Dorothea L. FLORIS, Auteur ; Christian F. BECKMANN, Auteur ; Jan K. BUITELAAR, Auteur . - 3p. Langues : Anglais (eng) in Molecular Autism > 15 (2024) . - 3p. Mots-clés : Humans  Gray Matter/diagnostic imaging  Autistic Disorder/diagnostic imaging  Autism Spectrum Disorder/diagnostic imaging  Retrospective Studies  Magnetic Resonance Imaging/methods  Brain/diagnostic imaging  Autism  Gray matter volume covariation  Replication  advisory board member of, and a speaker for Janssen Cilag BV, Eli Lilly, Shire,  Lundbeck, Roche, and Servier. He is not an employee of any of these companies,  and not a stock shareholder of any of these companies. He has no other financial  or material support, including expert testimony, patents or royalties. The  present work is unrelated to the above grants and relationships. The other  authors report no biomedical financial interests or potential conflicts of  interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (henceforth autism) is a complex neurodevelopmental condition associated with differences in gray matter (GM) volume covariations, as reported in our previous study of the Longitudinal European Autism Project (LEAP) data. To make progress on the identification of potential neural markers and to validate the robustness of our previous findings, we aimed to replicate our results using data from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) autism working group. METHODS: We studied 781 autistic and 927 non-autistic individuals (6-30 years, IQ?? 50), across 37 sites. Voxel-based morphometry was used to quantify GM volume as before. Subsequently, we used spatial maps of the two autism-related independent components (ICs) previously identified in the LEAP sample as templates for regression analyses to separately estimate the ENIGMA-participant loadings to each of these two ICs. Between-group differences in participants' loadings on each component were examined, and we additionally investigated the relation between participant loadings and autistic behaviors within the autism group. RESULTS: The two components of interest, previously identified in the LEAP dataset, showed significant between-group differences upon regressions into the ENIGMA cohort. The associated brain patterns were consistent with those found in the initial identification study. The first IC was primarily associated with increased volumes of bilateral insula, inferior frontal gyrus, orbitofrontal cortex, and caudate in the autism group relative to the control group (? = 0.129, p = 0.013). The second IC was related to increased volumes of the bilateral amygdala, hippocampus, and parahippocampal gyrus in the autism group relative to non-autistic individuals (? = 0.116, p = 0.024). However, when accounting for the site-by-group interaction effect, no significant main effect of the group can be identified (p > 0.590). We did not find significant univariate association between the brain measures and behavior in autism (p > 0.085). LIMITATIONS: The distributions of age, IQ, and sex between LEAP and ENIGMA are statistically different from each other. Owing to limited access to the behavioral data of the autism group, we were unable to further our understanding of the neural basis of behavioral dimensions of the sample. CONCLUSIONS: The current study is unable to fully replicate the autism-related brain patterns from LEAP in the ENIGMA cohort. The diverse group effects across ENIGMA sites demonstrate the challenges of generalizing the average findings of the GM covariation patterns to a large-scale cohort integrated retrospectively from multiple studies. Further analyses need to be conducted to gain additional insights into the generalizability of these two GM covariation patterns. En ligne : https://dx.doi.org/10.1186/s13229-024-00583-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=537

Auditory event-related potentials and associations with sensory patterns in children with autism spectrum disorder, developmental delay, and typical development / Franc C L. DONKERS in Autism, 24-5 (July 2020)  

Public ISBD [article]  inAutism > 24-5 (July 2020) . - p.1093-1110 Titre : Auditory event-related potentials and associations with sensory patterns in children with autism spectrum disorder, developmental delay, and typical development Type de document : texte imprimé Auteurs : Franc C L. DONKERS, Auteur ; Mike CARLSON, Auteur ; Sarah E. SCHIPUL, Auteur ; Aysenil BELGER, Auteur ; Grace T. BARANEK, Auteur Article en page(s) : p.1093-1110 Langues : Anglais (eng) Mots-clés : autism spectrum disorders  development  sensory impairments  interest. Index. décimale : PER Périodiques Résumé : Atypical sensory response patterns are common in children with autism and developmental delay. Expanding on previous work, this observational electroencephalogram study assessed auditory event-related potentials and their associations with clinically evaluated sensory response patterns in children with autism spectrum disorder (n = 28), developmental delay (n = 17), and typical development (n = 39). Attention-orienting P3a responses were attenuated in autism spectrum disorder relative to both developmental delay and typical development, but early sensory N2 responses were attenuated in both autism spectrum disorder and developmental delay relative to typical development. Attenuated event-related potentials involving N2 or P3a components, or a P1 × N2 interaction, were related to more severe hyporesponsive or sensory-seeking response patterns across children with autism spectrum disorder and developmental delay. Thus, although attentional disruptions may be unique to autism spectrum disorder, sensory disruptions appear across developmental delay and are associated with atypical sensory behaviors. En ligne : http://dx.doi.org/10.1177/1362361319893196 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=426 [article] Auditory event-related potentials and associations with sensory patterns in children with autism spectrum disorder, developmental delay, and typical development [texte imprimé] / Franc C L. DONKERS, Auteur ; Mike CARLSON, Auteur ; Sarah E. SCHIPUL, Auteur ; Aysenil BELGER, Auteur ; Grace T. BARANEK, Auteur . - p.1093-1110. Langues : Anglais (eng) in Autism > 24-5 (July 2020) . - p.1093-1110 Mots-clés : autism spectrum disorders  development  sensory impairments  interest. Index. décimale : PER Périodiques Résumé : Atypical sensory response patterns are common in children with autism and developmental delay. Expanding on previous work, this observational electroencephalogram study assessed auditory event-related potentials and their associations with clinically evaluated sensory response patterns in children with autism spectrum disorder (n = 28), developmental delay (n = 17), and typical development (n = 39). Attention-orienting P3a responses were attenuated in autism spectrum disorder relative to both developmental delay and typical development, but early sensory N2 responses were attenuated in both autism spectrum disorder and developmental delay relative to typical development. Attenuated event-related potentials involving N2 or P3a components, or a P1 × N2 interaction, were related to more severe hyporesponsive or sensory-seeking response patterns across children with autism spectrum disorder and developmental delay. Thus, although attentional disruptions may be unique to autism spectrum disorder, sensory disruptions appear across developmental delay and are associated with atypical sensory behaviors. En ligne : http://dx.doi.org/10.1177/1362361319893196 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=426

California Autism Prevalence by County and Race/Ethnicity: Declining Trends Among Wealthy Whites / Cynthia NEVISON in Journal of Autism and Developmental Disorders, 50-11 (November 2020)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 50-11 (November 2020) . - p.4011-4021 Titre : California Autism Prevalence by County and Race/Ethnicity: Declining Trends Among Wealthy Whites Type de document : texte imprimé Auteurs : Cynthia NEVISON, Auteur ; William PARKER, Auteur Article en page(s) : p.4011-4021 Langues : Anglais (eng) Mots-clés : Asian  Autism spectrum disorder  Black  California  County  Hispanic  Income  Prevalence  Race/ethnicity  Silicon Valley  Time trends  White  or financial relationships that could be construed as a potential conflict of  interest. Index. décimale : PER Périodiques Résumé : County-level ASD prevalence was estimated using an age-resolved snapshot from the California Department of Developmental Services (DDS) for birth years 1993-2013. ASD prevalence increased among all children across birth years 1993-2000 but plateaued or declined thereafter among whites from wealthy counties. In contrast, ASD rates increased continuously across 1993-2013 among whites from lower income counties and Hispanics from all counties. Both white ASD prevalence and rate of change in prevalence were inversely correlated to county income from birth year 2000-2013 but not 1993-2000. These disparate trends within the dataset suggest that wealthy white parents, starting around 2000, may have begun opting out of DDS in favor of private care and/or making changes that effectively lowered their children's risk of ASD. En ligne : http://dx.doi.org/10.1007/s10803-020-04460-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=432 [article] California Autism Prevalence by County and Race/Ethnicity: Declining Trends Among Wealthy Whites [texte imprimé] / Cynthia NEVISON, Auteur ; William PARKER, Auteur . - p.4011-4021. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 50-11 (November 2020) . - p.4011-4021 Mots-clés : Asian  Autism spectrum disorder  Black  California  County  Hispanic  Income  Prevalence  Race/ethnicity  Silicon Valley  Time trends  White  or financial relationships that could be construed as a potential conflict of  interest. Index. décimale : PER Périodiques Résumé : County-level ASD prevalence was estimated using an age-resolved snapshot from the California Department of Developmental Services (DDS) for birth years 1993-2013. ASD prevalence increased among all children across birth years 1993-2000 but plateaued or declined thereafter among whites from wealthy counties. In contrast, ASD rates increased continuously across 1993-2013 among whites from lower income counties and Hispanics from all counties. Both white ASD prevalence and rate of change in prevalence were inversely correlated to county income from birth year 2000-2013 but not 1993-2000. These disparate trends within the dataset suggest that wealthy white parents, starting around 2000, may have begun opting out of DDS in favor of private care and/or making changes that effectively lowered their children's risk of ASD. En ligne : http://dx.doi.org/10.1007/s10803-020-04460-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=432

eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy / Álvaro BELTRÁN-CORBELLINI in Journal of Neurodevelopmental Disorders, 17 (2025)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 17 (2025) Titre : eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy Type de document : texte imprimé Auteurs : Álvaro BELTRÁN-CORBELLINI, Auteur ; Adrián VALLS-CARBÓ, Auteur ; Rafael TOLEDANO, Auteur ; Irene GARCÍA-MORALES, Auteur ; Irene SÁNCHEZ-MIRANDA ROMÁN, Auteur ; Antonio GIL-NAGEL, Auteur Langues : Anglais (eng) Mots-clés : Humans  Eukaryotic Translation Initiation Factor 5A  Peptide Initiation Factors/genetics  Male  RNA-Binding Proteins/genetics  Mixed Function Oxygenases/genetics  Oxidoreductases Acting on CH-NH Group Donors/genetics  Female  Brain Diseases/genetics  Child, Preschool  Lysine/analogs & derivatives  Dhps  Dohh  Developmental and epileptic encephalopathy  Dravet syndrome  Eif5a  Eukaryotic translation factors  Febrile seizures  Fenfluramine  Refractory epilepsy  committee waived the need for approval regarding this case report. Consent for  publication: Written consent for publication was obtained from the parents of the  patient. Competing interests: ABC, RT, IGM, ISMR and AGN have received support  from, and served as paid consultants for UCB Pharma. AVC has no conflicts of  interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Eukaryotic initiation factor 5 A (eIF5A) and hypusination-related disorders (eIF5A-HRD) are recently described diseases caused by pathogenic heterozygous variants in the translation factor EIF5A or biallelic variants in the two enzymes involved in the post-translational synthesis of hypusine in the eIF5A precursor, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), necessary for its activation. We review the current knowledge regarding eIF5A-HRD, and report the case of the sixth and oldest known patient with DOHH-related disorder (DOHH-D), aiming to expand and discuss the molecular basis and the general and epilepsy phenotypes of this group of diseases. RESULTS: Literature review yielded one paper describing 7 individuals with eIF5A-related disorders (eIF5A-D), one reporting 5 subjects with DHPS-related disorders (DHPS-D) and one characterizing 5 individuals with DOHH-D. Main phenotypic features consisted of prenatal issues, hypotonia, dysmorphisms, microcephaly, moderate-severe neurodevelopmental disorders/intellectual disability and behavioral disorders. We report the case of a 24-years-old male with DOHH-D manifesting as Dravet-like syndrome. He displays microcephaly and neurodevelopmental delay with attention deficit with hyperactivity disorder, along with a happy demeanor. Basic language skills and ambulation capacity with crouch gait are preserved. Onset of epilepsy was at 8 months with refractory temperature-triggered hemiclonic seizures and status epilepticus, followed by nocturnal tonic-clonic seizures from adolescence. Fenfluramine was the most effective approach, reducing seizure intensity, duration and frequency, and contributing to cognitive and behavior improvements. No patient with eIF5A-D presented seizures. Taking our patient into account, 4/5 and 4/6 reported individuals with DHPS-D and DOHH-D, respectively, presented epilepsy. Seven out of 8 epilepsy patients debuted between 2 and 5 years, most of them presented developmental and epileptic encephalopathies or generalized epilepsies (5/8 with temperature or infection-triggered seizures), and 4/8 were refractory. We hypothesize that dysregulation of IQSEC2 and SHANK3, among other genes, might contribute to the eIF5A-HRD phenotype. CONCLUSIONS: eIF5A-HRD are recently described entities displaying neurodevelopmental disorders and microcephaly, and reported patients are scarce. More than 70% of DHPS-D and DOHH-D patients present epilepsy, 63% of them with temperature-triggered seizures. Valproic acid or fenfluramine may be effective. Rare homozygous or compound heterozygous missense variants in these genes should be screened in patients with encephalopathy and temperature-triggered seizures. En ligne : https://dx.doi.org/10.1186/s11689-025-09649-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576 [article] eIF5A and hypusination-related disorders: literature review and case report of DOHH-related encephalopathy [texte imprimé] / Álvaro BELTRÁN-CORBELLINI, Auteur ; Adrián VALLS-CARBÓ, Auteur ; Rafael TOLEDANO, Auteur ; Irene GARCÍA-MORALES, Auteur ; Irene SÁNCHEZ-MIRANDA ROMÁN, Auteur ; Antonio GIL-NAGEL, Auteur. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 17 (2025) Mots-clés : Humans  Eukaryotic Translation Initiation Factor 5A  Peptide Initiation Factors/genetics  Male  RNA-Binding Proteins/genetics  Mixed Function Oxygenases/genetics  Oxidoreductases Acting on CH-NH Group Donors/genetics  Female  Brain Diseases/genetics  Child, Preschool  Lysine/analogs & derivatives  Dhps  Dohh  Developmental and epileptic encephalopathy  Dravet syndrome  Eif5a  Eukaryotic translation factors  Febrile seizures  Fenfluramine  Refractory epilepsy  committee waived the need for approval regarding this case report. Consent for  publication: Written consent for publication was obtained from the parents of the  patient. Competing interests: ABC, RT, IGM, ISMR and AGN have received support  from, and served as paid consultants for UCB Pharma. AVC has no conflicts of  interest. Index. décimale : PER Périodiques Résumé : BACKGROUND: Eukaryotic initiation factor 5 A (eIF5A) and hypusination-related disorders (eIF5A-HRD) are recently described diseases caused by pathogenic heterozygous variants in the translation factor EIF5A or biallelic variants in the two enzymes involved in the post-translational synthesis of hypusine in the eIF5A precursor, deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH), necessary for its activation. We review the current knowledge regarding eIF5A-HRD, and report the case of the sixth and oldest known patient with DOHH-related disorder (DOHH-D), aiming to expand and discuss the molecular basis and the general and epilepsy phenotypes of this group of diseases. RESULTS: Literature review yielded one paper describing 7 individuals with eIF5A-related disorders (eIF5A-D), one reporting 5 subjects with DHPS-related disorders (DHPS-D) and one characterizing 5 individuals with DOHH-D. Main phenotypic features consisted of prenatal issues, hypotonia, dysmorphisms, microcephaly, moderate-severe neurodevelopmental disorders/intellectual disability and behavioral disorders. We report the case of a 24-years-old male with DOHH-D manifesting as Dravet-like syndrome. He displays microcephaly and neurodevelopmental delay with attention deficit with hyperactivity disorder, along with a happy demeanor. Basic language skills and ambulation capacity with crouch gait are preserved. Onset of epilepsy was at 8 months with refractory temperature-triggered hemiclonic seizures and status epilepticus, followed by nocturnal tonic-clonic seizures from adolescence. Fenfluramine was the most effective approach, reducing seizure intensity, duration and frequency, and contributing to cognitive and behavior improvements. No patient with eIF5A-D presented seizures. Taking our patient into account, 4/5 and 4/6 reported individuals with DHPS-D and DOHH-D, respectively, presented epilepsy. Seven out of 8 epilepsy patients debuted between 2 and 5 years, most of them presented developmental and epileptic encephalopathies or generalized epilepsies (5/8 with temperature or infection-triggered seizures), and 4/8 were refractory. We hypothesize that dysregulation of IQSEC2 and SHANK3, among other genes, might contribute to the eIF5A-HRD phenotype. CONCLUSIONS: eIF5A-HRD are recently described entities displaying neurodevelopmental disorders and microcephaly, and reported patients are scarce. More than 70% of DHPS-D and DOHH-D patients present epilepsy, 63% of them with temperature-triggered seizures. Valproic acid or fenfluramine may be effective. Rare homozygous or compound heterozygous missense variants in these genes should be screened in patients with encephalopathy and temperature-triggered seizures. En ligne : https://dx.doi.org/10.1186/s11689-025-09649-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=576

Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment / Kagistia Hana UTAMI in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 41 p. Titre : Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment Type de document : texte imprimé Auteurs : Kagistia Hana UTAMI, Auteur ; Nur Amirah Binte Mohammad YUSOF, Auteur ; Jing Eugene KWA, Auteur ; Ulla-Kaisa PETERI, Auteur ; Maija L. CASTRÉN, Auteur ; Mahmoud A. POULADI, Auteur Article en page(s) : 41 p. Langues : Anglais (eng) Mots-clés : Fragile X syndrome  Human stem cells  Protein synthesis  Therapy  interest. Index. décimale : PER Périodiques Résumé : FXS is the most common genetic cause of intellectual (ID) and autism spectrum disorders (ASD). FXS is caused by loss of FMRP, an RNA-binding protein involved in the translational regulation of a large number of neuronal mRNAs. Absence of FMRP has been shown to lead to elevated protein synthesis and is thought to be a major cause of the synaptic plasticity and behavioural deficits in FXS. The increase in protein synthesis results in part from abnormal activation of key protein translation pathways downstream of ERK1/2 and mTOR signalling. Pharmacological and genetic interventions that attenuate hyperactivation of these pathways can normalize levels of protein synthesis and improve phenotypic outcomes in animal models of FXS. Several efforts are currently underway to trial this strategy in patients with FXS. To date, elevated global protein synthesis as a result of FMRP loss has not been validated in the context of human neurons. Here, using an isogenic human stem cell-based model, we show that de novo protein synthesis is elevated in FMRP-deficient neural cells. We further show that this increase is associated with elevated ERK1/2 and Akt signalling and can be rescued by metformin treatment. Finally, we examined the effect of normalizing protein synthesis on phenotypic abnormalities in FMRP-deficient neural cells. We find that treatment with metformin attenuates the increase in proliferation of FMRP-deficient neural progenitor cells but not the neuronal deficits in neurite outgrowth. The elevated level of protein synthesis and the normalization of neural progenitor proliferation by metformin treatment were validated in additional control and FXS patient-derived hiPSC lines. Overall, our results validate that loss of FMRP results in elevated de novo protein synthesis in human neurons and suggest that approaches targeting this abnormality are likely to be of partial therapeutic benefit in FXS. En ligne : http://dx.doi.org/10.1186/s13229-020-00350-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 [article] Elevated de novo protein synthesis in FMRP-deficient human neurons and its correction by metformin treatment [texte imprimé] / Kagistia Hana UTAMI, Auteur ; Nur Amirah Binte Mohammad YUSOF, Auteur ; Jing Eugene KWA, Auteur ; Ulla-Kaisa PETERI, Auteur ; Maija L. CASTRÉN, Auteur ; Mahmoud A. POULADI, Auteur . - 41 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 41 p. Mots-clés : Fragile X syndrome  Human stem cells  Protein synthesis  Therapy  interest. Index. décimale : PER Périodiques Résumé : FXS is the most common genetic cause of intellectual (ID) and autism spectrum disorders (ASD). FXS is caused by loss of FMRP, an RNA-binding protein involved in the translational regulation of a large number of neuronal mRNAs. Absence of FMRP has been shown to lead to elevated protein synthesis and is thought to be a major cause of the synaptic plasticity and behavioural deficits in FXS. The increase in protein synthesis results in part from abnormal activation of key protein translation pathways downstream of ERK1/2 and mTOR signalling. Pharmacological and genetic interventions that attenuate hyperactivation of these pathways can normalize levels of protein synthesis and improve phenotypic outcomes in animal models of FXS. Several efforts are currently underway to trial this strategy in patients with FXS. To date, elevated global protein synthesis as a result of FMRP loss has not been validated in the context of human neurons. Here, using an isogenic human stem cell-based model, we show that de novo protein synthesis is elevated in FMRP-deficient neural cells. We further show that this increase is associated with elevated ERK1/2 and Akt signalling and can be rescued by metformin treatment. Finally, we examined the effect of normalizing protein synthesis on phenotypic abnormalities in FMRP-deficient neural cells. We find that treatment with metformin attenuates the increase in proliferation of FMRP-deficient neural progenitor cells but not the neuronal deficits in neurite outgrowth. The elevated level of protein synthesis and the normalization of neural progenitor proliferation by metformin treatment were validated in additional control and FXS patient-derived hiPSC lines. Overall, our results validate that loss of FMRP results in elevated de novo protein synthesis in human neurons and suggest that approaches targeting this abnormality are likely to be of partial therapeutic benefit in FXS. En ligne : http://dx.doi.org/10.1186/s13229-020-00350-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427

Impact of childhood maltreatment and resilience on behavioral and neural patterns of inhibitory control during emotional distraction / Lauren A. DEMERS in Development and Psychopathology, 34-4 (October 2022)  

Permalink

Incremental Utility of 24-Month Autism Spectrum Disorder Screening After Negative 18-Month Screening / Yael G. DAI in Journal of Autism and Developmental Disorders, 50-6 (June 2020)  

Permalink

Iterative redesign of a caregiver-mediated intervention for use in educational settings / Karen E. BEARSS in Autism, 26-3 (April 2022)  

Permalink

Model Teachers or Model Students? A Comparison of Video Modelling Interventions for Improving Reading Fluency and Comprehension in Children with Autism / Rachael EGARR in Journal of Autism and Developmental Disorders, 52-8 (August 2022)  

Permalink

Peri-Pregnancy Cannabis Use and Autism Spectrum Disorder in the Offspring: Findings from the Study to Explore Early Development / Carolyn G. DIGUISEPPI in Journal of Autism and Developmental Disorders, 52-11 (November 2022)  

Permalink