Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 77, Issue -, Pages 23-31Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2017.03.010
Keywords
Alzheimer's disease; Minocycline; Spatial memory; Neuroinflammation; Neurotrophins
Funding
- FAPESC
- Instituto Cerebro e Mente
- UNESC
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Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of age-related dementia. Cognitive decline, beta-amyloid (A beta) accumulation, neurofibrillary tangles, and neuroinflammation are the main pathophysiological characteristics of AD. Minocycline is a tetracycline derivative with anti-inflammatory properties that has a neuroprotective effect. The aim of this study was to evaluate the effect of minocycline on memory, neurotrophins and neuroinflammation in an animal model of AD induced by the administration of A beta (1-42) oligomer. Male BALB/c mice were treated with minocycline (50 mg/kg) via the oral route for a total of 17 days, 24 h after intracerebroventricular administration of A beta (1-42) oligomer. At the end of this period, was performed the radial maze test, and 24 h after the last minocycline administration, serum was collected and the cortex and hippocampus were dissected for biochemical analysis. The administration of minocycline reversed the memory impairment caused by A beta (1-42). In the hippocampus, minocycline reversed the increases in the levels of interleukin (IL-1 beta), Tumor Necrosis Factor-alpha (TNF-alpha) and, IL-10 caused by A beta (1-42). In the cortex, AD-like model increase the levels of IL-1D, TNF-beta and, IL-4. Minocycline treatment reversed this. In the serum, A beta (1-42) increased the levels of IL-1 beta and IL-4, and minocycline was able to reverse this action, but not to reverse the decrease of IL-10 levels. Minocycline also reversed the increase in the levels of Brain-derived neurotrophic factor (BDNF) in the hippocampus caused by A beta (1-42), and reduced Nerve Growth Factor (NGF) increases in the total cortex. Therefore, our results indicate that minocycline causes improvements in the spatial memory, and cytokine levels were correlated with this effect in the brain it. Besides this, minocydine reduced BDNF and NGF levels, highlighting the promising effects of minocycline in treating AD-like dementia.
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