Low Vitamin K Intake Impairs Cognition, Neurogenesis, and Elevates Neuroinflammation in C57BL/6 Mice

Background: 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. Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.