Lifetime consumption of a low vitamin K diet leads to learning impairment in aged rats: potential links with sphingolipid metabolism

Abstract

In a recent report, we showed VK to preferentially accumulate in brain regions rich in white matter and to positively correlate with certain sphingolipids. In rodents, pharmacological VK deficiency has resulted in behavioral perturbations. Whether a more physiological deficiency leads to similar effects has not yet been determined. To gain insight on this issue, we investigated learning abilities (Morris water maze) in 6, 12 and 20 month‐old female SD rats which had been fed diets containing either very low (VL: 80), low (L: 500) or moderately high (H: 2000) levels of K1 (μg/Kg diet; n=5–10/group) since weaning. In 20‐months rats, cerebroside, sulfatide, sphingomyelin, ceramide and gangliosides were also assessed in cerebellum, midbrain, pons medulla, striatum and hippocampus (Bodennec et al. Meth. Enzymol. 312:101–14, 2000). Lifetime consumption of a low VK diet led to cognitive deficits in old age, rats from VL group showing longer latencies to reach the platform than those from the L and H groups (p<0.05), a finding associated with higher concentrations of ceramides in the hippocampus and lower gangliosides in the pons medulla and midbrain. Learning abilities at 6 or 12 months were not affected by diet. In conclusion, we show for the first time that lifetime consumption of a low VK diet leads to learning impairments in old age and that this may be linked to disturbances in sphingolipid metabolism. Supported by NSERC.