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Energy metabolism disturbances in cell models of PARK2 CNV carriers with ADHD

Please always quote using this URN: urn:nbn:de:bvb:20-opus-220074
  • The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrientThe main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.show moreshow less

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Metadaten
Author: Viola Stella Palladino, Andreas G. Chiocchetti, Lukas Frank, Denise Haslinger, Rhiannon McNeill, Franziska Radtke, Andreas Till, Simone Haupt, Oliver Brüstle, Katharina Günther, Frank Edenhofer, Per Hoffmann, Andreas Reif, Sarah Kittel-Schneider
URN:urn:nbn:de:bvb:20-opus-220074
Document Type:Journal article
Faculties:Medizinische Fakultät / Klinik und Poliklinik für Kinder- und Jugendpsychiatrie, Psychosomatik und Psychotherapie
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie
Language:English
Parent Title (English):Journal of Clinical Medicine
ISSN:2077-0383
Year of Completion:2020
Volume:9
Issue:12
Article Number:4092
Source:Journal of Clinical Medicine (2020) 9:12, 4092. https://doi.org/10.3390/jcm9124092
DOI:https://doi.org/10.3390/jcm9124092
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:ADHD; PARK2; disease modelling; hiPSC; mitochondria
Release Date:2022/08/26
Date of first Publication:2020/12/18
EU-Project number / Contract (GA) number:643051
EU-Project number / Contract (GA) number:0800978
EU-Project number / Contract (GA) number:874758
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International