title: Methylene blue improves streptozotocin-induced memory deficit by restoring mitochondrial function in rats.
abstract: The pathogenesis of Alzheimer's disease (AD) is well documented to involve mitochondrial dysfunction which causes subsequent oxidative stress and energy metabolic failure in hippocampus. Methylene blue (MB) has been implicated to be neuroprotective in a variety of neurodegenerative diseases by restoring mitochondrial function. The present work was to examine if MB was able to improve streptozotocin (STZ)-induced Alzheimer's type dementia in a rat model by attenuating mitochondrial dysfunction-derived oxidative stress and ATP synthesis decline. MB was administrated at a dose of 0.5mg/kg/day for consecutive 7days after bilateral STZ intracerebroventricular (ICV) injection (2.5mg/kg). We first demonstrated that MB treatment significantly ameliorated STZ-induced hippocampus-dependent memory loss in passive avoidance test. We also found that MB has the properties to preserve neuron survival and attenuate neuronal degeneration in hippocampus CA1 region after STZ injection. In addition, oxidative stress was subsequently evaluated by measuring the content of lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE). Importantly, results from our study showed a remarkable suppression of MB treatment on both MDA production and 4-HNE immunoactivity. Finally, energy metabolism in CA1 region was examined by detecting mitochondrial cytochrome c oxidase (CCO) activity and the resultant ATP production. Of significant interest, our result displayed a robust facilitation of MB on CCO activity and the consequent ATP synthesis. The current study indicates that MB may be a promising therapeutic agent targeting oxidative damage and ATP synthesis failure during AD progression.
authors.affiliation: Department of Geriatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Geriatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Geriatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Hai-Long
authors.initials: HL
authors.lastname: Lu
authors.affiliation: Department of Geriatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China.
authors.forename: Ping-Jing
authors.initials: PJ
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China; Department of Genetics, Research Center for Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Song
authors.affiliation: Department of Geriatrics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, PR China. Electronic address: YRL6502@sina.com.
authors.forename: Rong-Li
authors.initials: RL
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D003576:Electron Transport Complex IV / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008751:Methylene Blue / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
chemical_list: D018696:Neuroprotective Agents; D018697:Nootropic Agents; D013311:Streptozocin; D000255:Adenosine Triphosphate; D003576:Electron Transport Complex IV; D008751:Methylene Blue
keywords: ATP synthesis decline; Alzheimer’s disease; Methylene blue; Mitochondrial dysfunction; Oxidative stress; Streptozotocin