Department of Medicine and Dermatology, Faculty of Medicine, University of Malaga, 29010 Malaga, Spain.
Trinity College Institute of Neuroscience, Trinity College Dublin, D02 DK07 Dublin, Ireland.
Cells. 2022 Feb 18;11(4):729. doi: 10.3390/cells11040729.
There is a striking sex-related difference in the prevalence of many neurodegenerative diseases, highlighting the need to consider whether treatments may exert sex-specific effects. A change in microglial activation state is a common feature of several neurodegenerative diseases and is considered to be a key factor in driving the inflammation that characterizes these conditions. Among the changes that have been described is a switch in microglial metabolism towards glycolysis which is associated with production of inflammatory mediators and reduced function. Marked sex-related differences in microglial number, phenotype and function have been described in late embryonic and early postnatal life in rodents and some reports suggest that sexual dimorphism extends into adulthood and age and, in models of Alzheimer's disease, the changes are more profound in microglia from female, compared with male, mice. Dimethyl fumarate (DMF) is a fumaric acid ester used in the treatment of psoriasis and relapsing remitting multiple sclerosis and, while its mechanism of action is unclear, it possesses anti-inflammatory and anti-oxidant properties and also impacts on cell metabolism. Here we treated 16-18-month-old female and male mice with DMF for 1 month and assessed its effect on microglia. The evidence indicates that it exerted sex-specific effects on microglial morphology and metabolism, reducing glycolysis only in microglia from female mice. The data suggest that this may result from its ability to inactivate glyceraldehyde-3-phosphate dehydrogenase (GAPDH).
在许多神经退行性疾病的患病率方面存在显著的性别差异，这突出表明需要考虑治疗方法是否可能产生特定于性别的影响。小胶质细胞激活状态的改变是几种神经退行性疾病的共同特征，被认为是驱动这些疾病特征性炎症的关键因素。已经描述的变化之一是小胶质细胞代谢向糖酵解的转变，这与炎症介质的产生和功能降低有关。在啮齿动物的晚期胚胎和早期新生期已经描述了小胶质细胞数量、表型和功能的显著性别差异，并且一些报告表明，性二态性延伸到成年期和年龄，并且在阿尔茨海默病模型中，与雄性小鼠相比，雌性小鼠的小胶质细胞变化更为深刻。富马酸二甲酯（DMF）是一种用于治疗银屑病和复发缓解型多发性硬化症的富马酸酯，尽管其作用机制尚不清楚，但它具有抗炎和抗氧化特性，并且还影响细胞代谢。在这里，我们用 DMF 治疗 16-18 个月大的雌性和雄性小鼠 1 个月，并评估了它对小胶质细胞的影响。证据表明，它对小胶质细胞形态和代谢产生了特定于性别的影响，仅降低了雌性小鼠小胶质细胞的糖酵解。数据表明，这可能是由于其能够使甘油醛-3-磷酸脱氢酶（GAPDH）失活。
