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

Abstract

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.

Objective: 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-month old C57BL/6 mice (n=60) were fed a LVK diet or a control diet for 6 months. Behavioral tests were performed on a subset of animals (n=26) at 15 months and brain tissues were collected for follow-up analyses.

Results: Menaquinone-4 (MK4), the predominant VK form in the brain, was significantly lower in LVK animals compared to controls (15.6±13.3 vs 189±186 pmol/g, respectively, p<0.01). LVK animals 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 vs. 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 animals had a significantly lower number of proliferating cells, and fewer newly generated immature neurons compared to control animals. Additionally, more activated microglia cells were identified in the LVK animals.

Conclusion: Our data indicate that LVK intake reduced MK4 levels 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.