Department of Physiology (Animal Physiology II), Faculty of Biology, Complutense University of Madrid, Madrid, Spain.
J Alzheimers Dis. 2011;25(4):727-37. doi: 10.3233/JAD-2011-110236.
We have previously shown that 3xTgAD mice (triple-transgenic mice for Alzheimer's disease, harboring PS1(M146V), AβPP(Swe), tau(P301L) transgenes) suffer detrimental changes in some key lymphocyte functions, described as health and longevity markers, with males being more affected than females and showing higher mortality rates. In the present work, 3xTgAD and wild type 129/C57BL6 male and female non- and environmentally enriched mice were used. The enriched environment (EE) began in the adulthood (6 months) and lasted for 5.5 months. The animals were sacrificed at advanced stages of the disease (15 month-old), and spleen, thymus, and plasma were obtained. The results indicate that 3xTg-AD males are especially benefitted from EE exposure, as shown by the improvement in lymphocyte functional activities such as chemotaxis and natural killer cytotoxicity, as well as in plasma corticosterone levels. By contrast, wild type females seem to be highly sensitive to EE removal, as regards the proliferation capacity of lymphocytes and their intracellular glutathione content. These results support the relevance of gender differences in AD when screening for new strategies for the control of the disease, and suggest that active life, by means of EE, should be maintained until natural death in order to preserve all the positive effects that this strategy exerts on the immune system.
我们之前已经表明，3xTgAD 小鼠（阿尔茨海默病的三转基因小鼠，携带 PS1（M146V）、AβPP（Swe）、tau（P301L）转基因）在一些关键的淋巴细胞功能上遭受有害的变化，这些变化被描述为健康和长寿的标志物，雄性比雌性受影响更大，死亡率更高。在本工作中，使用了 3xTgAD 和野生型 129/C57BL6 雄性和雌性非环境丰富和环境丰富的小鼠。丰富的环境（EE）始于成年期（6 个月），持续了 5.5 个月。在疾病的晚期（15 个月龄），对动物进行了安乐死，并获得了脾脏、胸腺和血浆。结果表明，3xTg-AD 雄性特别受益于 EE 暴露，如趋化性和自然杀伤细胞毒性等淋巴细胞功能活性的改善，以及血浆皮质酮水平的改善。相比之下，野生型雌性似乎对 EE 的去除非常敏感，因为淋巴细胞的增殖能力及其细胞内谷胱甘肽含量。这些结果支持在筛选控制疾病的新策略时考虑 AD 中的性别差异的相关性，并表明通过 EE 保持积极的生活方式直到自然死亡，以保持这种策略对免疫系统产生的所有积极影响。
