Garcez Michelle Lima, Mina Francielle, Bellettini-Santos Tatiani, Carneiro Franciellen Gonçalves, Luz Aline Pereira, Schiavo Gustavo Luis, Andrighetti Matheus Scopel, Scheid Maylton Grégori, Bolfe Renan Pereira, Budni Josiane
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Laboratory of Neurodegenerative Diseases, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil,; Laboratory of Neuroscience, Graduate Program in Health Sciences, Academic Unit of Health Sciences, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil..
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Jul 3;77:23-31. doi: 10.1016/j.pnpbp.2017.03.010. Epub 2017 Mar 21.
Alzheimer's disease (AD) is a neurodegenerative disorder and the most common type of age-related dementia. Cognitive decline, beta-amyloid (Aβ) 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 Aβ (1-42) oligomer. Male BALB/c mice were treated with minocycline (50mg/kg) via the oral route for a total of 17days, 24h after intracerebroventricular administration of Aβ (1-42) oligomer. At the end of this period, was performed the radial maze test, and 24h 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 Aβ (1-42). In the hippocampus, minocycline reversed the increases in the levels of interleukin (IL-1β), Tumor Necrosis Factor- alpha (TNF-α) and, IL-10 caused by Aβ (1-42). In the cortex, AD-like model increase the levels of IL-1β, TNF-α and, IL-4. Minocycline treatment reversed this. In the serum, Aβ (1-42) increased the levels of IL-1β 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 Aβ (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, minocycline reduced BDNF and NGF levels, highlighting the promising effects of minocycline in treating AD-like dementia.
阿尔茨海默病（AD）是一种神经退行性疾病，也是与年龄相关的最常见的痴呆类型。认知功能下降、β-淀粉样蛋白（Aβ）积累、神经原纤维缠结和神经炎症是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经Aβ（1-42）寡聚体给药诱导的AD动物模型的记忆、神经营养因子和神经炎症的影响。雄性BALB/c小鼠在脑室内注射Aβ（1-42）寡聚体24小时后，通过口服途径用米诺环素（50mg/kg）治疗，共17天。在此期间结束时，进行放射状迷宫试验，在最后一次给予米诺环素24小时后，收集血清，并解剖皮质和海马进行生化分析。米诺环素的给药逆转了由Aβ（1-42）引起的记忆障碍。在海马中，米诺环素逆转了由Aβ（1-42）引起的白细胞介素（IL-1β）、肿瘤坏死因子-α（TNF-α）和IL-10水平的升高。在皮质中，AD样模型增加了IL-1β、TNF-α和IL-4的水平。米诺环素治疗逆转了这一现象。在血清中，Aβ（1-42）增加了IL-1β和IL-4的水平，米诺环素能够逆转这一作用，但不能逆转IL-10水平的降低。米诺环素还逆转了由Aβ（1-42）引起的海马中脑源性神经营养因子（BDNF）水平的升高，并降低了整个皮质中神经生长因子（NGF）的升高。因此，我们的结果表明，米诺环素可改善空间记忆，且细胞因子水平与大脑中的这种作用相关。除此之外，米诺环素降低了BDNF和NGF水平，突出了米诺环素在治疗AD样痴呆方面的潜在作用。
