Hiramoto Keiichi, Yamate Yurika, Matsuda Kazunari, Sugiyama Daijiro, Iizuka Yasutaka
Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie 513-8670, Japan.
R&D Department, Daiichi Sankyo Healthcare Co., LTD, Shinagawa-ku, Tokyo 103-8234, Japan.
J Exp Pharmacol. 2020 Dec 18;12:653-663. doi: 10.2147/JEP.S284532. eCollection 2020.
Although the onset mechanism of Alzheimer's disease, which co-occurs with aging, has been extensively studied, no effective methods that improve the decline in memory and learning abilities following aging have been developed. Tranexamic acid provided promising results for ameliorating photo-aging and extending the natural lifespan. However, it is unknown whether it affects the decline in memory and learning abilities due to aging. In this study, we examined the effect of tranexamic acid on memory and learning abilities of naturally aging mice.
ICR mice were orally administered with tranexamic acid (12 mg/kg/day) three times weekly for 2 years, and their memory and learning abilities were compared between the tranexamic acid-treated and non-treated groups.
The decline in memory and learning abilities due to aging was ameliorated by tranexamic acid administration. The expression of plasmin and amyloid-β decreased following the treatment with tranexamic acid. Furthermore, the number of M1-type brain macrophages diminished and that of M2 macrophages increased. In addition, administration of tranexamic acid decreased the concentrations of interleukin (IL)-1β and tumor necrosis factor-α, while it increased the levels of IL-10 and transforming growth factor-α in the brain.
These results indicated that tranexamic acid suppressed the secretion of the inflammatory cytokines aging M1-type macrophages, thereby improving age-related memory and learning abilities.
尽管与衰老同时发生的阿尔茨海默病的发病机制已得到广泛研究,但尚未开发出有效方法来改善衰老后记忆和学习能力的下降。氨甲环酸在改善光老化和延长自然寿命方面取得了有前景的结果。然而,其是否会影响因衰老导致的记忆和学习能力下降尚不清楚。在本研究中,我们检测了氨甲环酸对自然衰老小鼠记忆和学习能力的影响。
将ICR小鼠每周口服氨甲环酸(12毫克/千克/天)3次,持续2年,并比较氨甲环酸处理组和未处理组小鼠的记忆和学习能力。
氨甲环酸给药改善了因衰老导致的记忆和学习能力下降。氨甲环酸处理后,纤溶酶和淀粉样β蛋白的表达降低。此外,M1型脑巨噬细胞数量减少,M2巨噬细胞数量增加。另外,氨甲环酸给药降低了大脑中白细胞介素(IL)-1β和肿瘤坏死因子-α的浓度,同时提高了IL-10和转化生长因子-α的水平。
这些结果表明,氨甲环酸抑制了衰老的M1型巨噬细胞分泌炎性细胞因子,从而改善了与年龄相关的记忆和学习能力。