Enriched vitamin K diet is associated with increased activation
of cell survival pathways in brains of young male rats, but has
no effect on cognition
Guylaine Ferland, Applied Physiology, Nutrition, and Metabolism 2020 Scientific Abstracts
Vitamin K accumulates in brain in the form of menaquinone-4, a
metabolite of phylloquinone (K1), the main dietary source. In addition
to its historic role in hemostasis, VK partakes in various cellular actions in brain and has been shown to modulate cognition. Notably, it
contributes to the biological activation of proteins Gas6 and protein S
(PS), both of which have been linked to extracellular signal-regulated
(ERK) and serine-threonine (Akt) kinases cell survival pathways. In a
previous study, lifetime high intakes of VK diet was associated with
increased cell survival signaling pathways and improved cognition in
aged male rats.
In this study, we tested whether similar positive effects
were observed earlier in life. Four-week old male Wistar rats were fed
an AIN-93 based diet containing either low 80 (L), adequate 750 (A) or
enriched 2000 (E) (mcg K1/kg/diet) diets for three months. K1 and MK-4
were measured by HPLC; PS and Gas6 carboxylation, ERK and Akt
phosphorylation, and BDNF expression were assessed in hippocampus (HPP), frontal cortex (FC) and striatum (STR), by immunoblotting.
Cognition was assessed using Morris water maze. Brain VK content
increased as a function of diet (p<0.01), MK-4 representing 84-99% of
total VK depending on diet. High VK intake was associated with increased carboxylated PS in STR (E vs L and A groups, p<0.01);
carboxylation of Gas6 was not affect by diet. Erk phosphorylation increased as function of dietary K1 in STR, in a dose dependent manner. Erk
activation was also higher in E and A groups compared to L group, in
HPP (both p<0.01). Likewise, Akt phosphorylation was systematically
lower in L vs E or A groups depending on brain region (p<0.02). Finally,
dietary VK had no impact on BDNF expression (p>0.2) and cognition
(p>0.5).
In conclusion, as observed in aged rats, an enriched vitamin K
diet is associated with increased cell survival signaling pathways in
young animals, although without providing additional benefit on cognition.
These results suggest that VK may be particularly beneficial to brain function in physiologically challenged animals such as those in
the aging state