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Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment.
Free Radic Biol Med. 2016 10; 99:11-19.FR

Abstract

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.

Authors+Show Affiliations

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, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Neuroscience, School of Advanced Science and Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.Department of Neuroscience, School of Advanced Science and Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27451936

Citation

Taghizadeh, Ghorban, et al. "Protective Effects of Physical Exercise On MDMA-induced Cognitive and Mitochondrial Impairment." Free Radical Biology & Medicine, vol. 99, 2016, pp. 11-19.
Taghizadeh G, Pourahmad J, Mehdizadeh H, et al. Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment. Free Radic Biol Med. 2016;99:11-19.
Taghizadeh, G., Pourahmad, J., Mehdizadeh, H., Foroumadi, A., Torkaman-Boutorabi, A., Hassani, S., Naserzadeh, P., Shariatmadari, R., Gholami, M., Rouini, M. R., & Sharifzadeh, M. (2016). Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment. Free Radical Biology & Medicine, 99, 11-19. https://doi.org/10.1016/j.freeradbiomed.2016.07.018
Taghizadeh G, et al. Protective Effects of Physical Exercise On MDMA-induced Cognitive and Mitochondrial Impairment. Free Radic Biol Med. 2016;99:11-19. PubMed PMID: 27451936.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment. AU - Taghizadeh,Ghorban, AU - Pourahmad,Jalal, AU - Mehdizadeh,Hajar, AU - Foroumadi,Alireza, AU - Torkaman-Boutorabi,Anahita, AU - Hassani,Shokoufeh, AU - Naserzadeh,Parvaneh, AU - Shariatmadari,Reyhaneh, AU - Gholami,Mahdi, AU - Rouini,Mohammad Reza, AU - Sharifzadeh,Mohammad, Y1 - 2016/07/21/ PY - 2016/02/25/received PY - 2016/07/13/revised PY - 2016/07/20/accepted PY - 2016/10/23/pubmed PY - 2017/12/30/medline PY - 2016/7/26/entrez KW - 3, 4-methylenedioxymethamphetamine (MDMA) KW - Cytochrome c KW - Learning and memory KW - Mitochondria KW - Oxidative stress KW - Physical exercise KW - ROS SP - 11 EP - 19 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 99 N2 - 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. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/27451936/Protective_effects_of_physical_exercise_on_MDMA_induced_cognitive_and_mitochondrial_impairment_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(16)30338-0 DB - PRIME DP - Unbound Medicine ER -