Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons / Emily M.A. LEWIS in Molecular Autism, 10 (2019)  

Public ISBD [article]  inMolecular Autism > 10 (2019) . - 51 p. Titre : Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons Type de document : texte imprimé Auteurs : Emily M.A. LEWIS, Auteur ; Kesavan MEGANATHAN, Auteur ; Dustin BALDRIDGE, Auteur ; Paul GONTARZ, Auteur ; Bo ZHANG, Auteur ; Azad BONNI, Auteur ; John N. CONSTANTINO, Auteur ; Kristen L. KROLL, Auteur Article en page(s) : 51 p. Langues : Anglais (eng) Mots-clés : Cortical excitatory neurons  Cortical inhibitory neurons  Gene networks  Multiplex autism  Neurodevelopment  Transcriptomics  iPSC modeling Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with pronounced heritability in the general population. This is largely attributable to the effects of polygenic susceptibility, with inherited liability exhibiting distinct sex differences in phenotypic expression. Attempts to model ASD in human cellular systems have principally involved rare de novo mutations associated with ASD phenocopies. However, by definition, these models are not representative of polygenic liability, which accounts for the vast share of population-attributable risk. Methods: Here, we performed what is, to our knowledge, the first attempt to model multiplex autism using patient-derived induced pluripotent stem cells (iPSCs) in a family manifesting incremental degrees of phenotypic expression of inherited liability (absent, intermediate, severe). The family members share an inherited variant of uncertain significance (VUS) in GPD2, a gene that was previously associated with developmental disability but here is insufficient by itself to cause ASD. iPSCs from three first-degree relatives and an unrelated control were differentiated into both cortical excitatory (cExN) and cortical inhibitory (cIN) neurons, and cellular phenotyping and transcriptomic analysis were conducted. Results: cExN neurospheres from the two affected individuals were reduced in size, compared to those derived from unaffected related and unrelated individuals. This reduction was, at least in part, due to increased apoptosis of cells from affected individuals upon initiation of cExN neural induction. Likewise, cIN neural progenitor cells from affected individuals exhibited increased apoptosis, compared to both unaffected individuals. Transcriptomic analysis of both cExN and cIN neural progenitor cells revealed distinct molecular signatures associated with affectation, including the misregulation of suites of genes associated with neural development, neuronal function, and behavior, as well as altered expression of ASD risk-associated genes. Conclusions: We have provided evidence of morphological, physiological, and transcriptomic signatures of polygenic liability to ASD from an analysis of cellular models derived from a multiplex autism family. ASD is commonly inherited on the basis of additive genetic liability. Therefore, identifying convergent cellular and molecular phenotypes resulting from polygenic and monogenic susceptibility may provide a critical bridge for determining which of the disparate effects of rare highly deleterious mutations might also apply to common autistic syndromes. En ligne : http://dx.doi.org/10.1186/s13229-019-0306-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414 [article] Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons [texte imprimé] / Emily M.A. LEWIS, Auteur ; Kesavan MEGANATHAN, Auteur ; Dustin BALDRIDGE, Auteur ; Paul GONTARZ, Auteur ; Bo ZHANG, Auteur ; Azad BONNI, Auteur ; John N. CONSTANTINO, Auteur ; Kristen L. KROLL, Auteur . - 51 p. Langues : Anglais (eng) in Molecular Autism > 10 (2019) . - 51 p. Mots-clés : Cortical excitatory neurons  Cortical inhibitory neurons  Gene networks  Multiplex autism  Neurodevelopment  Transcriptomics  iPSC modeling Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with pronounced heritability in the general population. This is largely attributable to the effects of polygenic susceptibility, with inherited liability exhibiting distinct sex differences in phenotypic expression. Attempts to model ASD in human cellular systems have principally involved rare de novo mutations associated with ASD phenocopies. However, by definition, these models are not representative of polygenic liability, which accounts for the vast share of population-attributable risk. Methods: Here, we performed what is, to our knowledge, the first attempt to model multiplex autism using patient-derived induced pluripotent stem cells (iPSCs) in a family manifesting incremental degrees of phenotypic expression of inherited liability (absent, intermediate, severe). The family members share an inherited variant of uncertain significance (VUS) in GPD2, a gene that was previously associated with developmental disability but here is insufficient by itself to cause ASD. iPSCs from three first-degree relatives and an unrelated control were differentiated into both cortical excitatory (cExN) and cortical inhibitory (cIN) neurons, and cellular phenotyping and transcriptomic analysis were conducted. Results: cExN neurospheres from the two affected individuals were reduced in size, compared to those derived from unaffected related and unrelated individuals. This reduction was, at least in part, due to increased apoptosis of cells from affected individuals upon initiation of cExN neural induction. Likewise, cIN neural progenitor cells from affected individuals exhibited increased apoptosis, compared to both unaffected individuals. Transcriptomic analysis of both cExN and cIN neural progenitor cells revealed distinct molecular signatures associated with affectation, including the misregulation of suites of genes associated with neural development, neuronal function, and behavior, as well as altered expression of ASD risk-associated genes. Conclusions: We have provided evidence of morphological, physiological, and transcriptomic signatures of polygenic liability to ASD from an analysis of cellular models derived from a multiplex autism family. ASD is commonly inherited on the basis of additive genetic liability. Therefore, identifying convergent cellular and molecular phenotypes resulting from polygenic and monogenic susceptibility may provide a critical bridge for determining which of the disparate effects of rare highly deleterious mutations might also apply to common autistic syndromes. En ligne : http://dx.doi.org/10.1186/s13229-019-0306-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=414

IPT English Reading & Writing Tests, Third Edition / Carol EZZELLE

Public ISBD contenu dans The Twenty-First Mental Measurements Yearbook / Janet F. CARLSON Titre : IPT English Reading & Writing Tests, Third Edition Type de document : texte imprimé Auteurs : Carol EZZELLE, Auteur ; Bo ZHANG, Auteur Année de publication : 2021 Importance : p.349-353 Langues : Anglais (eng) Index. décimale : OUT-A OUT-A - Outils d‘Evaluation - Tests Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=447 contenu dans The Twenty-First Mental Measurements Yearbook / Janet F. CARLSON IPT English Reading & Writing Tests, Third Edition [texte imprimé] / Carol EZZELLE, Auteur ; Bo ZHANG, Auteur . - 2021 . - p.349-353. Langues : Anglais (eng) Index. décimale : OUT-A OUT-A - Outils d‘Evaluation - Tests Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=447

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Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome / Michael G. MARISCAL in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 29 p. Titre : Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome Type de document : texte imprimé Auteurs : Michael G. MARISCAL, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; Lauren E ETHRIDGE, Auteur ; Rajna FILIP-DHIMA, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Alexander KOLEVZON, Auteur ; Meera E. MODI, Auteur ; Matthew W. MOSCONI, Auteur ; Charles A. NELSON, Auteur ; Craig M. POWELL, Auteur ; Paige M. SIPER, Auteur ; Latha SOORYA, Auteur ; Andrew THALIATH, Auteur ; Audrey THURM, Auteur ; Bo ZHANG, Auteur ; Mustafa SAHIN, Auteur ; April R. LEVIN, Auteur Article en page(s) : 29 p. Langues : Anglais (eng) Mots-clés : Cross-frequency coupling  Eeg  Phase bias  Phelan-McDermid syndrome  Power Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. METHODS: Here, we analyze EEG data collected across multiple sites in individuals with PMS (n = 26) and typically developing individuals (n = 15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. RESULTS: We find individuals with PMS display increased alpha-gamma phase bias (U = 3.841, p < 0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta = 0.545, p = 0.011). CONCLUSIONS: Increased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-020-00411-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Shifted phase of EEG cross-frequency coupling in individuals with Phelan-McDermid syndrome [texte imprimé] / Michael G. MARISCAL, Auteur ; Elizabeth BERRY-KRAVIS, Auteur ; Joseph D. BUXBAUM, Auteur ; Lauren E ETHRIDGE, Auteur ; Rajna FILIP-DHIMA, Auteur ; Jennifer H. FOSS-FEIG, Auteur ; Alexander KOLEVZON, Auteur ; Meera E. MODI, Auteur ; Matthew W. MOSCONI, Auteur ; Charles A. NELSON, Auteur ; Craig M. POWELL, Auteur ; Paige M. SIPER, Auteur ; Latha SOORYA, Auteur ; Andrew THALIATH, Auteur ; Audrey THURM, Auteur ; Bo ZHANG, Auteur ; Mustafa SAHIN, Auteur ; April R. LEVIN, Auteur . - 29 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 29 p. Mots-clés : Cross-frequency coupling  Eeg  Phase bias  Phelan-McDermid syndrome  Power Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid Syndrome (PMS) is a rare condition caused by deletion or mutation of the SHANK3 gene. Individuals with PMS frequently present with intellectual disability, autism spectrum disorder, and other neurodevelopmental challenges. Electroencephalography (EEG) can provide a window into network-level function in PMS. METHODS: Here, we analyze EEG data collected across multiple sites in individuals with PMS (n = 26) and typically developing individuals (n = 15). We quantify oscillatory power, alpha-gamma phase-amplitude coupling strength, and phase bias, a measure of the phase of cross frequency coupling thought to reflect the balance of feedforward (bottom-up) and feedback (top-down) activity. RESULTS: We find individuals with PMS display increased alpha-gamma phase bias (U = 3.841, p < 0.0005), predominantly over posterior electrodes. Most individuals with PMS demonstrate positive overall phase bias while most typically developing individuals demonstrate negative overall phase bias. Among individuals with PMS, strength of alpha-gamma phase-amplitude coupling was associated with Sameness, Ritualistic, and Compulsive behaviors as measured by the Repetitive Behavior Scales-Revised (Beta = 0.545, p = 0.011). CONCLUSIONS: Increased phase bias suggests potential circuit-level mechanisms underlying phenotype in PMS, offering opportunities for back-translation of findings into animal models and targeting in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-020-00411-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

Social-valence-related increased attention in rett syndrome cynomolgus monkeys: An eye-tracking study / Bo ZHANG in Autism Research, 12-11 (November 2019)  

Public ISBD [article]  inAutism Research > 12-11 (November 2019) . - p.1585-1597 Titre : Social-valence-related increased attention in rett syndrome cynomolgus monkeys: An eye-tracking study Type de document : texte imprimé Auteurs : Bo ZHANG, Auteur ; Zhigang ZHOU, Auteur ; Yin ZHOU, Auteur ; Tian ZHANG, Auteur ; Yuanye MA, Auteur ; Yuyu NIU, Auteur ; Weizhi JI, Auteur ; Yongchang CHEN, Auteur Article en page(s) : p.1585-1597 Langues : Anglais (eng) Mots-clés : Rett syndrome  animal models  attention  cognitive neuroscience  visual Index. décimale : PER Périodiques Résumé : The cognitive phenotypes of Rett syndrome (RTT) remain unclarified compared with the well-defined genetic etiology. Recent clinical studies suggest the eye-tracking method as a promising avenue to quantify the visual phenotypes of the syndrome. The present study explored various aspects of visual attention of the methyl-CpG-binding protein 2 gene mutant RTT monkeys with the eye-tracking procedure. Comprehensive testing paradigms, including social valence comparison (SVC), visual paired comparison (VPC), and social recognition memory (SRM), were utilized to investigate their attentional features to social stimuli with differential valence, the novelty preferences, and short-term recognition memory, respectively. To explore the neurobiological mechanisms underlying the eye-tracking findings, we assessed changes of the brain subregion volumes and neurotransmitter concentrations. Compared with control monkeys, RTT monkeys demonstrated increased viewing on the more salient stare faces than profile faces in the SVC test, and increased viewing on the whole presented images composed of monkey faces in the VPC and SRM tests. Brain imaging revealed reduced bilateral occipital gyrus in RTT monkeys. The exploratory neurotransmitter analyses revealed no significant changes of various neurotransmitter concentrations in the cerebrospinal fluid and blood of RTT monkeys. The eye-tracking results suggested social-valence-related increased attention in RTT monkeys, supplementing the cognitive phenotypes associated with the syndrome. Further investigations from broader perspectives are required to uncover the underlying neurobiological mechanisms. Autism Res 2019, 00: 1-13. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Altered expressions of the methyl-CpG-binding protein 2 (MECP2) gene are usually associated with neurodevelopmental disorders, such as autism spectrum disorders, Rett syndrome (RTT), and so forth. The present eye-tracking study found social-valence-related increased attention in our firstly established MECP2 mutant RTT monkeys. The novel findings supplement the cognitive phenotypes and potentially benefit the behavioral interventions of the RTT syndrome. En ligne : http://dx.doi.org/10.1002/aur.2189 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=411 [article] Social-valence-related increased attention in rett syndrome cynomolgus monkeys: An eye-tracking study [texte imprimé] / Bo ZHANG, Auteur ; Zhigang ZHOU, Auteur ; Yin ZHOU, Auteur ; Tian ZHANG, Auteur ; Yuanye MA, Auteur ; Yuyu NIU, Auteur ; Weizhi JI, Auteur ; Yongchang CHEN, Auteur . - p.1585-1597. Langues : Anglais (eng) in Autism Research > 12-11 (November 2019) . - p.1585-1597 Mots-clés : Rett syndrome  animal models  attention  cognitive neuroscience  visual Index. décimale : PER Périodiques Résumé : The cognitive phenotypes of Rett syndrome (RTT) remain unclarified compared with the well-defined genetic etiology. Recent clinical studies suggest the eye-tracking method as a promising avenue to quantify the visual phenotypes of the syndrome. The present study explored various aspects of visual attention of the methyl-CpG-binding protein 2 gene mutant RTT monkeys with the eye-tracking procedure. Comprehensive testing paradigms, including social valence comparison (SVC), visual paired comparison (VPC), and social recognition memory (SRM), were utilized to investigate their attentional features to social stimuli with differential valence, the novelty preferences, and short-term recognition memory, respectively. To explore the neurobiological mechanisms underlying the eye-tracking findings, we assessed changes of the brain subregion volumes and neurotransmitter concentrations. Compared with control monkeys, RTT monkeys demonstrated increased viewing on the more salient stare faces than profile faces in the SVC test, and increased viewing on the whole presented images composed of monkey faces in the VPC and SRM tests. Brain imaging revealed reduced bilateral occipital gyrus in RTT monkeys. The exploratory neurotransmitter analyses revealed no significant changes of various neurotransmitter concentrations in the cerebrospinal fluid and blood of RTT monkeys. The eye-tracking results suggested social-valence-related increased attention in RTT monkeys, supplementing the cognitive phenotypes associated with the syndrome. Further investigations from broader perspectives are required to uncover the underlying neurobiological mechanisms. Autism Res 2019, 00: 1-13. (c) 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Altered expressions of the methyl-CpG-binding protein 2 (MECP2) gene are usually associated with neurodevelopmental disorders, such as autism spectrum disorders, Rett syndrome (RTT), and so forth. The present eye-tracking study found social-valence-related increased attention in our firstly established MECP2 mutant RTT monkeys. The novel findings supplement the cognitive phenotypes and potentially benefit the behavioral interventions of the RTT syndrome. En ligne : http://dx.doi.org/10.1002/aur.2189 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=411

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