Universität zu Köln

Palladino, Viola Stella, Chiocchetti, Andreas G., Frank, Lukas, Haslinger, Denise, McNeill, Rhiannon, Radtke, Franziska, Till, Andreas, Haupt, Simone, Bruestle, Oliver, Guenther, Katharina, Edenhofer, Frank, Hoffmann, Per, Reif, Andreas and Kittel-Schneider, Sarah ORCID: 0000-0003-3057-6150 (2020). Energy Metabolism Disturbances in Cell Models of PARK2 CNV Carriers with ADHD. J. Clin. Med., 9 (12). BASEL: MDPI. ISSN 2077-0383

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Palladino, Viola Stella UNSPECIFIED UNSPECIFIED UNSPECIFIED Chiocchetti, Andreas G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frank, Lukas UNSPECIFIED UNSPECIFIED UNSPECIFIED Haslinger, Denise UNSPECIFIED UNSPECIFIED UNSPECIFIED McNeill, Rhiannon UNSPECIFIED UNSPECIFIED UNSPECIFIED Radtke, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Till, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Haupt, Simone UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruestle, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Guenther, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Edenhofer, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoffmann, Per UNSPECIFIED UNSPECIFIED UNSPECIFIED Reif, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Kittel-Schneider, Sarah UNSPECIFIED orcid.org/0000-0003-3057-6150 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-309612
DOI:	10.3390/jcm9124092
Journal or Publication Title:	J. Clin. Med.
Volume:	9
Number:	12
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2077-0383
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEFICIT-HYPERACTIVITY DISORDER; MITOCHONDRIAL DYSFUNCTION; PARKINSON DISEASE; REGULATORS; UBIQUITIN; STRESS; IMPACT; PINK1 Multiple languages Medicine, General & Internal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30961