Centre d'Information et de documentation du CRA Rhône-Alpes
CRA
Informations pratiques
-
Adresse
Centre d'information et de documentation
du CRA Rhône-Alpes
Centre Hospitalier le Vinatier
bât 211
95, Bd Pinel
69678 Bron CedexHoraires
Lundi au Vendredi
9h00-12h00 13h30-16h00Contact
Tél: +33(0)4 37 91 54 65
Mail
Fax: +33(0)4 37 91 54 37
-
Détail de l'auteur
Auteur S. THACKER |
Documents disponibles écrits par cet auteur (2)
Faire une suggestion Affiner la recherche
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