Low vitamin K intake negatively affects cognition and hippocampal neurogenesis in C57 BL6 mice

Authors: ZHENG, TONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FU, XUEYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SHEN, XIAOHUA - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MARSCHALL, SHANNON - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; SMITH, DONALD - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; TARR, ANDREW - Tufts University; MYKYTEN, KATHRYN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; BIEDERER, THOMAS - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Shukitt-Hale, Barbara; BOOTH, SARAH - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/3/2023
Publication Date: 7/22/2023
Citation: Zheng, T., Fu, X., Shen, X., Marschall, S., Smith, D., Tarr, A., Mykyten, K., Biederer, T., Shukitt Hale, B., Booth, S. 2023. Low vitamin K intake negatively affects cognition and hippocampal neurogenesis in C57 BL6 mice. [Abstract]. 7(Suppl 1):101202. https://doi.org/10.1016/j.cdnut.2023.101202.
DOI: https://doi.org/10.1016/j.cdnut.2023.101202

Interpretive Summary:

Technical Abstract: Objectives: Low dietary vitamin K (VK) intake, which is common among older adults, is associated with age-related dementia and cognitive impairment. Aging and neurodegenerative diseases negatively affect hippocampal neurogenesis, which results in cognitive deficits such as in learning and memory. To elucidate the cellular and molecular mechanisms underlying these effects, we leveraged a mouse model to investigate the effects of low VK intake on cognition and neurogenesis within the dentate gyrus, the area in hippocampus that is involved in neurogenesis and regulation of learning and memory. Methods: Middle-aged (7-9 mo) C57 BL6 mice (Charles River, n=60) were randomly assigned by weight to four groups (n=15/group): low vitamin K males and females (LVKM and LVKF, 80µg phylloquinone (PK)/kg diet), control diet males and females (CM and CF, 1mg PK/kg diet). All animals were fed ad lib for 6 mo. At the end of feeding period, behavioral tests were performed on all animals and brain tissue was collected for follow-up analyses. Brain VK contents, including PK and menaquinone-4 (MK4, the predominant PK metabolite found in the brain), were measured using HPLC. Hippocampal neurogenesis was evaluated with markers of proliferation (Ki67) and of newly generated hippocampal neurons (Doublecortin). Positive cells were quantified per hippocampal section and compared among experimental groups. Results: MK4, the predominant VK form in the brain, was significantly lower in LVK animals compared to controls (15.6±4.7 vs. 189.0±65.8 pmol/g, p<0.001). LVK animals also showed reduced recognition memory on the novel object task compared to controls. Within the hippocampal dentate gyrus, LVK animals had significantly lower Ki67 positive cells (12.14±1.25 vs. 22.75±3.6/section, p=0.01), and fewer doublecortin positive cells (113±17.8 vs. 294.6±43.4/section, p=0.007), compared to control animals. Conclusions: Low VK intake impaired learning- and memory-related cognitive function; reduced MK4 content in brain tissues; and significantly reduced hippocampal neurogenesis. These data suggested that low VK diets may lead to cognitive impairment through decreased hippocampal neurogenesis and availability of MK4 in the brain.