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

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 th
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 (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.
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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:hebis:30:3-572212
DOI:http://dx.doi.org/10.3390/jcm9124092
ISSN:2077-0383
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=33353000
Parent Title (German):Journal of clinical medicine
Publisher:MDPI
Place of publication:Basel
Document Type:Article
Language:English
Date of Publication (online):2020/12/18
Date of first Publication:2020/12/18
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/01/11
Tag:ADHD; PARK2; disease modelling; hiPSC; mitochondria
Volume:9
Issue:Article 4092
Pagenumber:20
Institutes:Medizin
Dewey Decimal Classification:610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Licence (German):License LogoCreative Commons - Namensnennung 4.0

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