Energy Metabolism Disturbances in Cell Models of PARK2 CNV Carriers with ADHD

Journal of Clinical Medicine, 2020 · DOI: 10.3390/jcm9124092 · Published: December 18, 2020

Simple Explanation

This study investigates cellular models derived from ADHD patients with copy number variants (CNVs) in the PARK2 gene, which is linked to mitochondrial function and energy metabolism. The researchers examined how these PARK2 CNVs affect mitochondrial function, ATP production, oxygen consumption, and reactive oxygen species in human fibroblasts and dopamine neurons. The findings suggest an energy impairment in cells of PARK2 CNV carriers with ADHD, potentially linked to the role of PARK2 in mitochondrial dynamics.

Study Duration

Not specified

Participants

Four ADHD patients and two healthy controls

Evidence Level

Not specified

Key Findings

1
Changes were found in PARK2 gene and protein expression in PARK2 CNV deletion and duplication carriers with ADHD compared to controls.
2
PARK2 CNV carriers with ADHD showed altered ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines.
3
The PARK2 CNV duplication carrier/ADHD cells exhibit a pronounced elongated mitochondrial shape and tubular branching.

Research Summary

The study aimed to identify cellular phenotypes in ADHD patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus. Human-derived fibroblasts (HDF) and human-induced pluripotent stem cells (hiPSC) differentiated into dopaminergic neuronal cells (mDANs) were used to assess mitochondrial function and energy metabolism under baseline and stress conditions. The results suggest an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD, potentially associated with PARK2 dysregulation in mitochondrial dynamics.

Practical Implications

Therapeutic Options

Substances that increase mitochondrial functions and decrease oxidative stress, such as antioxidants (e.g., polyphenols), should be investigated as potential treatments for ADHD.

Understanding Neurodevelopmental Diseases

The findings highlight the role of PARK2 and PINK1 in mitochondrial quality control and their potential functional role in psychiatric and neurodevelopmental disorders like ADHD.

Vulnerability to Stress

ADHD PARK2 CNV deletion and duplication carrier cells show a stronger vulnerability to nutrient deprivation stress, suggesting a potential target for intervention.

Study Limitations

1
Low number of biological repeats (patients and controls), especially in the mDAN, and no isogenic controls.
2
PARK2 CNVs represent a rare variation found just in a small subset of ADHD patients.
3
Electrophysiological experiments were not conducted to investigate basal neuronal functions.

Your Feedback

Was this summary helpful?

Back to Mental Health