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.

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.