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Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function.
Behav Brain Res. 2017 01 01; 316:115-124.BB

Abstract

Oxidative stress and mitochondrial dysfunction play indispensable role in memory and learning impairment. Growing evidences have shed light on anti-oxidative role for melatonin in memory deficit. We have previously reported that inhibition of protein kinase A by H-89 can induce memory impairment. Here, we investigated the effect of melatonin on H-89 induced spatial memory deficit and pursued their interactive consequences on oxidative stress and mitochondrial function in Morris Water Maze model. Rats received melatonin (50 and 100μg/kg/side) and H-89(10μM) intra-hippocampally 30min before each day of training. Animals were trained for 4 consecutive days, each containing one block from four trials. Oxidative stress indices, including thiobarbituric acid (TBARS), reactive oxygen species (ROS), thiol groups, and ferric reducing antioxidant power (FRAP) were assessed using spectrophotometer. Mitochondrial function was evaluated through measuring ROS production, mitochondrial membrane potential (MMP), swelling, outer membrane damage, and cytochrome c release. As expected from our previous report, H-89 remarkably impaired memory by increasing the escape latency and traveled distance. Intriguingly, H-89 significantly augmented TBARS and ROS levels, caused mitochondrial ROS production, swelling, outer membrane damage, and cytochrome c release. Moreover, H-89 lowered thiol, FRAP, and MMP values. Intriguingly, melatonin pre-treatment not only effectively hampered H-89-mediated spatial memory deficit at both doses, but also reversed the H-89 effects on mitochondrial and biochemical indices upon higher dose. Collectively, these findings highlight a protective role for melatonin against H-89-induced memory impairment and indicate that melatonin may play a therapeutic role in the treatment of oxidative- related neurodegenerative disorders.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran; College of Pharmacy, University of Manitoba, 750 McDermot Avenue, Winnipeg, R3E 0T5, MB, Canada; Manitoba Multiple Sclerosis Research Network Organization (MMSRNO), Winnipeg, Canada.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.Department of Neuroscience, School of Advanced Science and Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.Leslie Dan Faculty of Pharmacy, Department of Pharmaceutical Sciences, University of Toronto, M5S 3M2, Toronto, ON, Canada.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, P.O. Box 14155-6451, Tehran, Iran. Electronic address: msharifzadeh@tums.ac.ir.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27555536

Citation

Sharif, Rojin, et al. "Melatonin Reverses H-89 Induced Spatial Memory Deficit: Involvement of Oxidative Stress and Mitochondrial Function." Behavioural Brain Research, vol. 316, 2017, pp. 115-124.
Sharif R, Aghsami M, Gharghabi M, et al. Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function. Behav Brain Res. 2017;316:115-124.
Sharif, R., Aghsami, M., Gharghabi, M., Sanati, M., Khorshidahmad, T., Vakilzadeh, G., Mehdizadeh, H., Gholizadeh, S., Taghizadeh, G., & Sharifzadeh, M. (2017). Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function. Behavioural Brain Research, 316, 115-124. https://doi.org/10.1016/j.bbr.2016.08.040
Sharif R, et al. Melatonin Reverses H-89 Induced Spatial Memory Deficit: Involvement of Oxidative Stress and Mitochondrial Function. Behav Brain Res. 2017 01 1;316:115-124. PubMed PMID: 27555536.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function. AU - Sharif,Rojin, AU - Aghsami,Mehdi, AU - Gharghabi,Mehdi, AU - Sanati,Mehdi, AU - Khorshidahmad,Tina, AU - Vakilzadeh,Gelareh, AU - Mehdizadeh,Hajar, AU - Gholizadeh,Shervin, AU - Taghizadeh,Ghorban, AU - Sharifzadeh,Mohammad, Y1 - 2016/08/21/ PY - 2016/04/29/received PY - 2016/08/11/revised PY - 2016/08/20/accepted PY - 2016/8/25/pubmed PY - 2017/11/29/medline PY - 2016/8/25/entrez KW - Hippocampus KW - Melatonin KW - Mitochondrial function KW - Oxidative stress KW - Protein kinase A KW - Spatial memory SP - 115 EP - 124 JF - Behavioural brain research JO - Behav Brain Res VL - 316 N2 - Oxidative stress and mitochondrial dysfunction play indispensable role in memory and learning impairment. Growing evidences have shed light on anti-oxidative role for melatonin in memory deficit. We have previously reported that inhibition of protein kinase A by H-89 can induce memory impairment. Here, we investigated the effect of melatonin on H-89 induced spatial memory deficit and pursued their interactive consequences on oxidative stress and mitochondrial function in Morris Water Maze model. Rats received melatonin (50 and 100μg/kg/side) and H-89(10μM) intra-hippocampally 30min before each day of training. Animals were trained for 4 consecutive days, each containing one block from four trials. Oxidative stress indices, including thiobarbituric acid (TBARS), reactive oxygen species (ROS), thiol groups, and ferric reducing antioxidant power (FRAP) were assessed using spectrophotometer. Mitochondrial function was evaluated through measuring ROS production, mitochondrial membrane potential (MMP), swelling, outer membrane damage, and cytochrome c release. As expected from our previous report, H-89 remarkably impaired memory by increasing the escape latency and traveled distance. Intriguingly, H-89 significantly augmented TBARS and ROS levels, caused mitochondrial ROS production, swelling, outer membrane damage, and cytochrome c release. Moreover, H-89 lowered thiol, FRAP, and MMP values. Intriguingly, melatonin pre-treatment not only effectively hampered H-89-mediated spatial memory deficit at both doses, but also reversed the H-89 effects on mitochondrial and biochemical indices upon higher dose. Collectively, these findings highlight a protective role for melatonin against H-89-induced memory impairment and indicate that melatonin may play a therapeutic role in the treatment of oxidative- related neurodegenerative disorders. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/27555536/Melatonin_reverses_H_89_induced_spatial_memory_deficit:_Involvement_of_oxidative_stress_and_mitochondrial_function_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(16)30558-7 DB - PRIME DP - Unbound Medicine ER -