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BBA Clin. 2016 Oct 18;6:153-158. eCollection 2016 Dec.

Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction.

Author information

1
CSIR-Indian Institute of Chemical Biology, Laboratory of Clinical & Experimental Neurosciences, Cell Biology & Physiology Division, 4, Raja S.C. Mullick Road, Kolkata - 700032, India.
2
Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482, Madudah, Sector-J, Eastern Metropolitan Bypass, Kolkata 700 017, India.
3
CSIR-Indian Institute of Chemical Biology, Laboratory of Clinical & Experimental Neurosciences, Cell Biology & Physiology Division, 4, Raja S.C. Mullick Road, Kolkata - 700032, India; Inter University Centre for Biomedical Research & Super Specialty Hospital, Mahatma Gandhi University Campus at Thalappady, Rubber Board PO, Kottayam - 686009, Kerala State, India.

Abstract

BACKGROUND:

Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population.

METHODS:

To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ0-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry. HPLC-electrochemical detection, quantitative RT-PCR and Blue Native PAGE were employed respectively for assays of serotonin, mitochondrial ATPase 6/8 subunits levels and complex V activity.

RESULTS:

Significantly low cellular and mitochondrial respiration, ATPase6/8 transcripts levels, mitochondrial complex V activity and loss of mitochondrial membrane potential and elevated oxidative stress were observed in ADHD cybrids. Expression of monoamine oxidizing mitochondrial enzymes, MAO-A and MAO-B levels remained unaffected. Two-fold increase in serotonin level was noted in differentiated cybrid-neurons.

CONCLUSIONS:

Since cybrids are shown to replicate mitochondrial defects seen in post-mortem brains, these observed defects in ADHD cybrids strongly suggest mitochondrial pathology in this disorder.

GENERAL SIGNIFICANCE:

Mitochondrial defects are detected in ADHD cybrids created from patients' platelets, implying bioenergetics crisis in the mitochondria could be a contributory factor for ADHD pathology and/or phenotypes.

KEYWORDS:

ATPase; Cybrids; Mitochondrial membrane potential; Mitochondrial pathology; Respiration; Serotonin

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