title: Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Laboratory of Clinical & Experimental Neurosciences, Cell Biology & Physiology Division, 4, Raja S.C. Mullick Road, Kolkata - 700032, India.
authors.forename: Poonam
authors.initials: P
authors.lastname: Verma
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Laboratory of Clinical & Experimental Neurosciences, Cell Biology & Physiology Division, 4, Raja S.C. Mullick Road, Kolkata - 700032, India.
authors.forename: Alpana
authors.initials: A
authors.lastname: Singh
authors.affiliation: CSIR-Indian Institute of Chemical Biology, Laboratory of Clinical & Experimental Neurosciences, Cell Biology & Physiology Division, 4, Raja S.C. Mullick Road, Kolkata - 700032, India.
authors.forename: Dominic Ngima
authors.initials: DN
authors.lastname: Nthenge-Ngumbau
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482, Madudah, Sector-J, Eastern Metropolitan Bypass, Kolkata 700 017, India.
authors.forename: Usha
authors.initials: U
authors.lastname: Rajamma
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482, Madudah, Sector-J, Eastern Metropolitan Bypass, Kolkata 700 017, India.
authors.forename: Swagata
authors.initials: S
authors.lastname: Sinha
authors.affiliation: Manovikas Biomedical Research and Diagnostic Centre, Manovikas Kendra, 482, Madudah, Sector-J, Eastern Metropolitan Bypass, Kolkata 700 017, India.
authors.forename: Kanchan
authors.initials: K
authors.lastname: Mukhopadhyay
authors.affiliation: 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.
authors.forename: Kochupurackal P
authors.initials: KP
authors.lastname: Mohanakumar
keywords: ATPase; Cybrids; Mitochondrial membrane potential; Mitochondrial pathology; Respiration; Serotonin