Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study / Axel KRUG in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 54 p. Titre : Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study Type de document : Texte imprimé et/ou numérique Auteurs : Axel KRUG, Auteur ; Markus WÖHR, Auteur ; Dominik SEFFER, Auteur ; Henrike RIPPBERGER, Auteur ; A. Özge SUNGUR, Auteur ; Bruno DIETSCHE, Auteur ; Frederike STEIN, Auteur ; Sugirthan SIVALINGAM, Auteur ; Andreas J. FORSTNER, Auteur ; Stephanie H. WITT, Auteur ; Helene DUKAL, Auteur ; Fabian STREIT, Auteur ; Anna MAASER, Auteur ; Stefanie HEILMANN-HEIMBACH, Auteur ; Till F. M. ANDLAUER, Auteur ; Stefan HERMS, Auteur ; Per HOFFMANN, Auteur ; Marcella RIETSCHEL, Auteur ; Markus M. NÖTHEN, Auteur ; Martin LACKINGER, Auteur ; Gerhard SCHRATT, Auteur ; Michael KOCH, Auteur ; Rainer K. W. SCHWARTING, Auteur ; Tilo KIRCHER, Auteur Article en page(s) : 54 p. Langues : Anglais (eng) Mots-clés : Advanced paternal age (APA)  Diffusion tension imaging (DTI)  Social behavior  Ultrasonic vocalization  Voxel-based morphometry (VBM) Index. décimale : PER Périodiques Résumé : Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction. En ligne : http://dx.doi.org/10.1186/s13229-020-00345-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 [article] Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study [Texte imprimé et/ou numérique] / Axel KRUG, Auteur ; Markus WÖHR, Auteur ; Dominik SEFFER, Auteur ; Henrike RIPPBERGER, Auteur ; A. Özge SUNGUR, Auteur ; Bruno DIETSCHE, Auteur ; Frederike STEIN, Auteur ; Sugirthan SIVALINGAM, Auteur ; Andreas J. FORSTNER, Auteur ; Stephanie H. WITT, Auteur ; Helene DUKAL, Auteur ; Fabian STREIT, Auteur ; Anna MAASER, Auteur ; Stefanie HEILMANN-HEIMBACH, Auteur ; Till F. M. ANDLAUER, Auteur ; Stefan HERMS, Auteur ; Per HOFFMANN, Auteur ; Marcella RIETSCHEL, Auteur ; Markus M. NÖTHEN, Auteur ; Martin LACKINGER, Auteur ; Gerhard SCHRATT, Auteur ; Michael KOCH, Auteur ; Rainer K. W. SCHWARTING, Auteur ; Tilo KIRCHER, Auteur . - 54 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 54 p. Mots-clés : Advanced paternal age (APA)  Diffusion tension imaging (DTI)  Social behavior  Ultrasonic vocalization  Voxel-based morphometry (VBM) Index. décimale : PER Périodiques Résumé : Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction. En ligne : http://dx.doi.org/10.1186/s13229-020-00345-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427

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