Melatonin Reverses H-89 Induced Spatial Memory Deficit: Involvement of Oxidative Stress and Mitochondrial Function Publisher Pubmed



Sharif R¹ ; Aghsami M¹ ; Gharghabi M¹ ; Sanati M¹ ; Khorshidahmad T^{1, 2, 3} ; Vakilzadeh G¹ ; Mehdizadeh H⁴ ; Gholizadeh S⁵ ; Taghizadeh G⁴ ; Sharifzadeh M¹ Show Affiliations
Source: Behavioural Brain Research Published:2017

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 100 μg/kg/side) and H-89(10 μM) intra-hippocampally 30 min 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. © 2016 Elsevier B.V.