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Auteur C. ENG |
Documents disponibles écrits par cet auteur (3)
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Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations / M. ULJAREVIC in Journal of Autism and Developmental Disorders, 52-1 (January 2022)
[article]
Titre : Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations Type de document : Texte imprimé et/ou numérique Auteurs : M. ULJAREVIC, Auteur ; T. W. FRAZIER, Auteur ; G. RACHED, Auteur ; Robyn M. BUSCH, Auteur ; P. KLAAS, Auteur ; S. SRIVASTAVA, Auteur ; J. A. MARTINEZ-AGOSTO, Auteur ; M. SAHIN, Auteur ; C. ENG, Auteur ; A. Y. HARDAN, Auteur Article en page(s) : p.414-422 Langues : Anglais (eng) Mots-clés : Anxiety/genetics Autism Spectrum Disorder/genetics Child Child, Preschool Germ Cells Germ-Line Mutation Humans PTEN Phosphohydrolase/genetics Parents Anxiety Executive functioning Insistence on sameness Macrocephaly Pten Index. décimale : PER Périodiques Résumé : This study aimed to characterize the relationship between insistence on sameness (IS), executive functioning (EF) and anxiety among individuals with PTEN mutations and individuals with macrocephalic ASD. The sample included 38 individuals with PTEN mutation and ASD diagnosis (PTEN-ASD; M(age)?=?8.93 years, SD(age)?=?4.75), 23 with PTEN mutation without ASD (PTEN-no ASD; M(age)?=?8.94 years; SD(age)?=?4.85) and 25 with ASD and macrocephaly but with no PTEN mutation (Macro-ASD; M(age)?=?11.99 years; SD(age)?=?5.15). The final model accounted for 45.7% of variance in IS, with Set-Shifting EF subdomain as a unique independent predictor (t?=?4.12, p?0.001). This investigation provides the first preliminary evidence for the EF-anxiety-IS interrelationship in individuals with PTEN mutations and with macrocephalic ASD. En ligne : http://dx.doi.org/10.1007/s10803-021-04881-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455
in Journal of Autism and Developmental Disorders > 52-1 (January 2022) . - p.414-422[article] Brief Report: Role of Parent-Reported Executive Functioning and Anxiety in Insistence on Sameness in Individuals with Germline PTEN Mutations [Texte imprimé et/ou numérique] / M. ULJAREVIC, Auteur ; T. W. FRAZIER, Auteur ; G. RACHED, Auteur ; Robyn M. BUSCH, Auteur ; P. KLAAS, Auteur ; S. SRIVASTAVA, Auteur ; J. A. MARTINEZ-AGOSTO, Auteur ; M. SAHIN, Auteur ; C. ENG, Auteur ; A. Y. HARDAN, Auteur . - p.414-422.
Langues : Anglais (eng)
in Journal of Autism and Developmental Disorders > 52-1 (January 2022) . - p.414-422
Mots-clés : Anxiety/genetics Autism Spectrum Disorder/genetics Child Child, Preschool Germ Cells Germ-Line Mutation Humans PTEN Phosphohydrolase/genetics Parents Anxiety Executive functioning Insistence on sameness Macrocephaly Pten Index. décimale : PER Périodiques Résumé : This study aimed to characterize the relationship between insistence on sameness (IS), executive functioning (EF) and anxiety among individuals with PTEN mutations and individuals with macrocephalic ASD. The sample included 38 individuals with PTEN mutation and ASD diagnosis (PTEN-ASD; M(age)?=?8.93 years, SD(age)?=?4.75), 23 with PTEN mutation without ASD (PTEN-no ASD; M(age)?=?8.94 years; SD(age)?=?4.85) and 25 with ASD and macrocephaly but with no PTEN mutation (Macro-ASD; M(age)?=?11.99 years; SD(age)?=?5.15). The final model accounted for 45.7% of variance in IS, with Set-Shifting EF subdomain as a unique independent predictor (t?=?4.12, p?0.001). This investigation provides the first preliminary evidence for the EF-anxiety-IS interrelationship in individuals with PTEN mutations and with macrocephalic ASD. En ligne : http://dx.doi.org/10.1007/s10803-021-04881-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=455 Erratum to: Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits / X. HE in Molecular Autism, 7 (2016)
[article]
Titre : Erratum to: Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits Type de document : Texte imprimé et/ou numérique Auteurs : X. HE, Auteur ; S. THACKER, Auteur ; T. ROMIGH, Auteur ; Q. YU, Auteur ; T. W. FRAZIER, Auteur ; C. ENG, Auteur Article en page(s) : 14p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-015-0056-6.]. En ligne : http://dx.doi.org/10.1186/s13229-016-0075-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328
in Molecular Autism > 7 (2016) . - 14p.[article] Erratum to: Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits [Texte imprimé et/ou numérique] / X. HE, Auteur ; S. THACKER, Auteur ; T. ROMIGH, Auteur ; Q. YU, Auteur ; T. W. FRAZIER, Auteur ; C. ENG, Auteur . - 14p.
Langues : Anglais (eng)
in Molecular Autism > 7 (2016) . - 14p.
Index. décimale : PER Périodiques Résumé : [This corrects the article DOI: 10.1186/s13229-015-0056-6.]. En ligne : http://dx.doi.org/10.1186/s13229-016-0075-y Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328 Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity / N. SARN in Molecular Autism, 12 (2021)
[article]
Titre : Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity Type de document : Texte imprimé et/ou numérique Auteurs : N. SARN, Auteur ; S. THACKER, Auteur ; H. LEE, Auteur ; C. ENG, Auteur Article en page(s) : 41 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder Complement Microglia Mouse model Neurodegeneration Neuroinflammation Oxytocin PTEN mutation Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) has a strong genetic etiology. Germline mutation in the tumor suppressor gene PTEN is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific Pten loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior. As such, there is a growing need to understand more about how various aspects of PTEN activity and cell-compartment-specific functions, contribute to certain neurological or behavior phenotypes. METHODS: To understand more about the relationship between Pten localization and downstream effects on neurophenotypes, we generated the nuclear-predominant Pten(Y68H/+) mouse, which is identical to the genotype of some PTEN-ASD individuals. We subjected the Pten(Y68H/+) mouse to morphological and behavioral phenotyping, including the three-chamber sociability, open field, rotarod, and marble burying tests. We subsequently performed in vivo and in vitro cellular phenotyping and concluded the work with a transcriptomic survey of the Pten(Y68H/+) cortex, which profiled gene expression. RESULTS: We observe a significant increase in P-Akt downstream of canonical Pten signaling, macrocephaly, decreased sociability, decreased preference for novel social stimuli, increased repetitive behavior, and increased thigmotaxis in Pten(Y68H/+) six-week-old (P40) mice. In addition, we found significant microglial activation with increased expression of complement and neuroinflammatory proteins in vivo and in vitro accompanied by enhanced phagocytosis. These observations were subsequently validated with RNA-seq and qRT-PCR, which revealed overexpression of many genes involved in neuroinflammation and neuronal function, including oxytocin. Oxytocin transcript was fivefold overexpressed (P?=?0.0018), and oxytocin protein was strongly overexpressed in the Pten(Y68H/+) hypothalamus. CONCLUSIONS: The nuclear-predominant Pten(Y68H/+) model has clarified that Pten dysfunction links to microglial pathology and this associates with increased Akt signaling. We also demonstrate that Pten dysfunction associates with changes in the oxytocin system, an important connection between a prominent ASD risk gene and a potent neuroendocrine regulator of social behavior. These cellular and molecular pathologies may related to the observed changes in social behavior. Ultimately, the findings from this work may reveal important biomarkers and/or novel therapeutic modalities that could be explored in individuals with germline mutations in PTEN with ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00448-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 41 p.[article] Germline nuclear-predominant Pten murine model exhibits impaired social and perseverative behavior, microglial activation, and increased oxytocinergic activity [Texte imprimé et/ou numérique] / N. SARN, Auteur ; S. THACKER, Auteur ; H. LEE, Auteur ; C. ENG, Auteur . - 41 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 41 p.
Mots-clés : Autism spectrum disorder Complement Microglia Mouse model Neurodegeneration Neuroinflammation Oxytocin PTEN mutation Social impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) has a strong genetic etiology. Germline mutation in the tumor suppressor gene PTEN is one of the best described monogenic risk cases for ASD. Animal modeling of cell-specific Pten loss or mutation has provided insight into how disruptions to the function of PTEN affect neurodevelopment, neurobiology, and social behavior. As such, there is a growing need to understand more about how various aspects of PTEN activity and cell-compartment-specific functions, contribute to certain neurological or behavior phenotypes. METHODS: To understand more about the relationship between Pten localization and downstream effects on neurophenotypes, we generated the nuclear-predominant Pten(Y68H/+) mouse, which is identical to the genotype of some PTEN-ASD individuals. We subjected the Pten(Y68H/+) mouse to morphological and behavioral phenotyping, including the three-chamber sociability, open field, rotarod, and marble burying tests. We subsequently performed in vivo and in vitro cellular phenotyping and concluded the work with a transcriptomic survey of the Pten(Y68H/+) cortex, which profiled gene expression. RESULTS: We observe a significant increase in P-Akt downstream of canonical Pten signaling, macrocephaly, decreased sociability, decreased preference for novel social stimuli, increased repetitive behavior, and increased thigmotaxis in Pten(Y68H/+) six-week-old (P40) mice. In addition, we found significant microglial activation with increased expression of complement and neuroinflammatory proteins in vivo and in vitro accompanied by enhanced phagocytosis. These observations were subsequently validated with RNA-seq and qRT-PCR, which revealed overexpression of many genes involved in neuroinflammation and neuronal function, including oxytocin. Oxytocin transcript was fivefold overexpressed (P?=?0.0018), and oxytocin protein was strongly overexpressed in the Pten(Y68H/+) hypothalamus. CONCLUSIONS: The nuclear-predominant Pten(Y68H/+) model has clarified that Pten dysfunction links to microglial pathology and this associates with increased Akt signaling. We also demonstrate that Pten dysfunction associates with changes in the oxytocin system, an important connection between a prominent ASD risk gene and a potent neuroendocrine regulator of social behavior. These cellular and molecular pathologies may related to the observed changes in social behavior. Ultimately, the findings from this work may reveal important biomarkers and/or novel therapeutic modalities that could be explored in individuals with germline mutations in PTEN with ASD. En ligne : http://dx.doi.org/10.1186/s13229-021-00448-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459