Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function
| Autor: | Ghorban Taghizadeh, Gelareh Vakilzadeh, Tina Khorshidahmad, Mehdi Gharghabi, Mehdi Sanati, Mehdi Aghsami, Mohammad Sharifzadeh, Shervin Gholizadeh, Hajar Mehdizadeh, Rojin Sharif |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Xylazine 0301 basic medicine Mitochondrial ROS medicine.medical_specialty Antioxidant medicine.medical_treatment Morris water navigation task Oxidative phosphorylation Biology medicine.disease_cause Hippocampus Antioxidants Melatonin 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Escape Reaction Internal medicine Reaction Time medicine TBARS Animals Hypnotics and Sedatives Rats Wistar Protein Kinase Inhibitors Membrane Potential Mitochondrial chemistry.chemical_classification Memory Disorders Sulfonamides Reactive oxygen species Cytochromes c Isoquinolines Mitochondria Rats Disease Models Animal 030104 developmental biology Endocrinology chemistry Lipid Peroxidation Reactive Oxygen Species 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | Behavioural Brain Research. 316:115-124 |
| ISSN: | 0166-4328 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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