Minocycline reduces inflammatory parameters in the brain structures and serum and reverses memory impairment caused by the administration of amyloid β (1-42) in mice
Minocycline reduces inflammatory parameters in the brain structures and serum and reverses memory impairment caused by the administration of amyloid β (1-42) in mice
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DOI：
10.1016/j.pnpbp.2017.03.010
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发表时间：
2017-07-03
影响因子：
5.6
通讯作者：
Budni, Josiane
中科院分区：
文献类型：
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作者：
Garcez, Michelle Lima;Mina, Francielle;Budni, Josiane
阿尔茨海默病（AD）是一种神经退行性疾病，也是最常见的年龄相关性痴呆。认知功能下降、β-淀粉样蛋白（A β）蓄积、神经元缠结和神经炎症是AD的主要病理生理特征。米诺环素是一种具有抗炎特性的四环素衍生物，具有神经保护作用。本研究的目的是评估米诺环素对A β（1-42）寡聚体诱导的AD动物模型中记忆、神经营养因子和神经炎症的影响。在脑室内施用A β（1-42）寡聚体后24小时，通过口服途径用米诺环素（50 mg/kg）处理雄性BALB/c小鼠总共17天。在此阶段结束时，进行径向迷宫测试，并在最后一次米诺环素给药后24 h，收集血清，解剖皮质和海马用于生化分析。米诺环素的给药逆转了A β（1-42）引起的记忆障碍。在海马中，米诺环素逆转了A β引起的白细胞介素（IL-1 β）、肿瘤坏死因子-α（TNF-α）和IL-10水平的升高（1-42）。在皮质，AD样模型增加IL-1D、TNF-β和IL-4的水平。米诺环素治疗逆转了这一点。在血清中，A β（1-42）增加IL-1 β和IL-4的水平，米诺环素能够逆转这种作用，但不能逆转IL-10水平的下降。米诺环素还逆转了A β（1-42）引起的海马中脑源性神经营养因子（BDNF）水平的增加，并减少了总皮质中神经生长因子（NGF）的增加。因此，我们的研究结果表明，二甲胺四环素导致空间记忆的改善，细胞因子水平与这种效果在大脑中，除此之外，二甲胺四环素降低BDNF和NGF水平，突出了二甲胺四环素在治疗AD样痴呆的有希望的效果。
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.