Zheng Tong, Marschall Shannon, Weinberg Jasper, Fu Xueyan, Tarr Andrew, Shukitt-Hale Barbara, Booth Sarah L
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States.
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, United States.
J Nutr. 2025 Apr;155(4):1119-1126. doi: 10.1016/j.tjnut.2025.01.023. Epub 2025 Jan 28.
In addition to its important roles in blood coagulation and bone formation, vitamin K (VK) contributes to brain function. Low dietary VK intake, which is common among older adults, is associated with age-related cognitive impairment.
To elucidate the biological mechanisms underlying VK's effects on cognition, we investigated the effects of low VK (LVK) intake on cognition in C57BL/6 mice.
Male and female 9-mo-old C57BL/6 mice (n = 60) were fed an LVK diet or a control diet for 6 mo. Behavioral tests were performed on a subset of mice (n = 26) at 15 mo, and brain tissues were collected for follow-up analyses.
Menaquinone-4, the predominant VK form in the brain, was significantly lower in LVK mice compared to controls (15.6 ± 13.3 compared with 189 ± 186 pmol/g, respectively, P < 0.01). LVK mice showed reduced recognition memory in the novel object test by spending a lower percentage of time exploring the novel object compared to controls (47.45% ± 4.17 compared with 58.08% ± 3.03, P = 0.04). They also spent a significantly longer time learning the task of locating the platform in the Morris water maze test. Within the hippocampal dentate gyrus, LVK mice had a significantly lower number of proliferating cells and fewer newly generated immature neurons compared to control mice. Additionally, more activated microglia cells were identified in the LVK mice.
Our data indicate that LVK intake reduced menaquinone-4 concentrations in brain tissues and impaired learning- and memory-related cognitive function. This impairment may be related to the observed reduced hippocampal neurogenesis and elevated neural inflammation.
除了在血液凝固和骨骼形成中发挥重要作用外，维生素K（VK）对脑功能也有贡献。老年人中常见的低膳食VK摄入量与年龄相关的认知障碍有关。
为阐明VK对认知影响的生物学机制，我们研究了低VK（LVK）摄入量对C57BL/6小鼠认知的影响。
将9月龄的雄性和雌性C57BL/6小鼠（n = 60）分别喂食LVK饮食或对照饮食6个月。在15月龄时对一部分小鼠（n = 26）进行行为测试，并收集脑组织进行后续分析。
脑内主要的VK形式甲基萘醌-4，LVK小鼠显著低于对照组（分别为15.6±13.3与189±186 pmol/g，P < 0.01）。与对照组相比，LVK小鼠在新物体测试中识别记忆能力下降，探索新物体的时间百分比更低（47.45%±4.17与58.08%±3.03，P = 0.04）。在莫里斯水迷宫测试中，它们学习定位平台任务的时间也显著更长。在海马齿状回内，与对照小鼠相比，LVK小鼠的增殖细胞数量显著减少，新生成的未成熟神经元数量也更少。此外，在LVK小鼠中发现更多活化的小胶质细胞。
我们的数据表明，摄入LVK会降低脑组织中甲基萘醌-4的浓度，并损害与学习和记忆相关的认知功能。这种损害可能与观察到的海马神经发生减少和神经炎症增加有关。
