PMID- 27451936 OWN - NLM STAT- MEDLINE DCOM- 20171229 LR - 20181202 IS - 1873-4596 (Electronic) IS - 0891-5849 (Linking) VI - 99 DP - 2016 Oct TI - Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment. PG - 11-19 LID - S0891-5849(16)30338-0 [pii] LID - 10.1016/j.freeradbiomed.2016.07.018 [doi] AB - Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Taghizadeh, Ghorban AU - Taghizadeh G AD - Department of Neuroscience, School of Advanced Science and Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Pourahmad, Jalal AU - Pourahmad J AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Mehdizadeh, Hajar AU - Mehdizadeh H AD - Department of Neuroscience, School of Advanced Science and Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Foroumadi, Alireza AU - Foroumadi A AD - Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. FAU - Torkaman-Boutorabi, Anahita AU - Torkaman-Boutorabi A AD - Department of Neuroscience, School of Advanced Science and Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran. FAU - Hassani, Shokoufeh AU - Hassani S AD - Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. FAU - Naserzadeh, Parvaneh AU - Naserzadeh P AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. FAU - Shariatmadari, Reyhaneh AU - Shariatmadari R AD - Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. FAU - Gholami, Mahdi AU - Gholami M AD - Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. FAU - Rouini, Mohammad Reza AU - Rouini MR AD - Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. FAU - Sharifzadeh, Mohammad AU - Sharifzadeh M AD - Department of Neuroscience, School of Advanced Science and Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: msharifzadeh@sina.tums.ac.ir. LA - eng PT - Journal Article DEP - 20160721 PL - United States TA - Free Radic Biol Med JT - Free radical biology & medicine JID - 8709159 RN - 0 (Reactive Oxygen Species) RN - 61D2G4IYVH (Adenosine Diphosphate) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - 9007-43-6 (Cytochromes c) RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) SB - IM MH - Adenosine Diphosphate/metabolism MH - Adenosine Triphosphate/antagonists & inhibitors/metabolism MH - Animals MH - Brain/drug effects/metabolism/physiopathology MH - Cognitive Dysfunction/chemically induced/metabolism/physiopathology/*prevention & control MH - Cytochromes c/metabolism MH - Dose-Response Relationship, Drug MH - Injections, Intraperitoneal MH - Male MH - Maze Learning/*drug effects MH - Membrane Potential, Mitochondrial/drug effects MH - Mitochondria/*drug effects/metabolism/pathology MH - Mitochondrial Swelling/drug effects MH - N-Methyl-3,4-methylenedioxyamphetamine/administration & dosage/*toxicity MH - Oxidative Stress MH - *Physical Conditioning, Animal MH - Rats MH - Rats, Wistar MH - Reactive Oxygen Species/agonists/metabolism MH - Spatial Memory/*drug effects OTO - NOTNLM OT - 3, 4-methylenedioxymethamphetamine (MDMA) OT - Cytochrome c OT - Learning and memory OT - Mitochondria OT - Oxidative stress OT - Physical exercise OT - ROS EDAT- 2016/10/23 06:00 MHDA- 2017/12/30 06:00 CRDT- 2016/07/26 06:00 PHST- 2016/02/25 00:00 [received] PHST- 2016/07/13 00:00 [revised] PHST- 2016/07/20 00:00 [accepted] PHST- 2016/10/23 06:00 [pubmed] PHST- 2017/12/30 06:00 [medline] PHST- 2016/07/26 06:00 [entrez] AID - S0891-5849(16)30338-0 [pii] AID - 10.1016/j.freeradbiomed.2016.07.018 [doi] PST - ppublish SO - Free Radic Biol Med. 2016 Oct;99:11-19. doi: 10.1016/j.freeradbiomed.2016.07.018. Epub 2016 Jul 21.