Selective activation of anti-inflammatory type 2 microglia as a strategy for treatment of Alzheimer's disease

在这项研究中，我们试图开发种子来刺激抗炎2型小胶质细胞的神经保护活性，作为治疗阿尔茨海默病的新策略。我们专注于合成维甲酸，因为据报道，它们可以增加T细胞系统中IL-4的产生。(1)给予维甲酸可显著改善APP23小鼠的记忆缺陷，并降低脑内不溶性Aβ肽的水平。(2)与赋形剂治疗组相比，维甲酸治疗组大鼠大脑皮层IL-4水平升高，而海马区IL-4水平升高。此外，APP23小鼠在接受维甲酸治疗后记忆力的改善与海马区IL-4水平有关。(3)在体外，维甲酸共同刺激小鼠小胶质细胞MG5后，IL-4Rα表达增加。这些发现提供了有关这些药物对AD的治疗潜力的信息。

In this study, we tried to develop seeds that stimulate the neuro-protective activities of anti-inflammatory type 2 microglia as a new strategy for treatment of Alzheimer’s disease. We focused on synthetic retinoids, because they have reported to increase IL-4 production in T-cell system. (1) Administration of the retinoids significantly improved memory deficits in APP23 mice and reduced levels of insoluble Aβ peptide in the brain. (2) IL-4 level in the hippocampus, not in the cerebral cortex, tended to increase in retinoids-treated group compared with vehicle-treated one. In addition, improvement of memory in APP23 mice after retinoid treatment was related to the IL-4 level in the hippocampus. (3) In vitro, IL-4R α was increased in murine microglial MG5 cells co-stimulated with retinoids. These findings provide information about the therapeutic potential of these agents for AD.