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Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121149/ https://www.ncbi.nlm.nih.gov/pubmed/27896136 http://dx.doi.org/10.1016/j.bbacli.2016.10.003 |
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author | Verma, Poonam Singh, Alpana Nthenge-Ngumbau, Dominic Ngima Rajamma, Usha Sinha, Swagata Mukhopadhyay, Kanchan Mohanakumar, Kochupurackal P |
author_facet | Verma, Poonam Singh, Alpana Nthenge-Ngumbau, Dominic Ngima Rajamma, Usha Sinha, Swagata Mukhopadhyay, Kanchan Mohanakumar, Kochupurackal P |
author_sort | Verma, Poonam |
collection | PubMed |
description | 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 ρ(0)-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. |
format | Online Article Text |
id | pubmed-5121149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-51211492016-11-28 Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction Verma, Poonam Singh, Alpana Nthenge-Ngumbau, Dominic Ngima Rajamma, Usha Sinha, Swagata Mukhopadhyay, Kanchan Mohanakumar, Kochupurackal P BBA Clin Regular Article 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 ρ(0)-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. Elsevier 2016-10-18 /pmc/articles/PMC5121149/ /pubmed/27896136 http://dx.doi.org/10.1016/j.bbacli.2016.10.003 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Regular Article Verma, Poonam Singh, Alpana Nthenge-Ngumbau, Dominic Ngima Rajamma, Usha Sinha, Swagata Mukhopadhyay, Kanchan Mohanakumar, Kochupurackal P Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction |
title | Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction |
title_full | Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction |
title_fullStr | Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction |
title_full_unstemmed | Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction |
title_short | Attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction |
title_sort | attention deficit-hyperactivity disorder suffers from mitochondrial dysfunction |
topic | Regular Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121149/ https://www.ncbi.nlm.nih.gov/pubmed/27896136 http://dx.doi.org/10.1016/j.bbacli.2016.10.003 |
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