Age-dependent survival-promoting activity of vitamin K on cultured CNS neurons

Neurons from the central nervous system (CNS) of rat embryos die within several days when seeded at a low density of 10(4) cells/cm2 and cultured in a serum-free defined medium. Using these culture systems, we searched for agents to promote the survival of these neurons. As a consequence, a fat-soluble vitamin, vitamin K1, was found to possess such kind of activity: more than 50% of the cortical neurons from 19-day-old rat embryos could survive for 4 days in the presence of vitamin K1, whereas almost all neurons died in its absence. The survival-promoting effect of vitamin K1 was found on neurons from not only cortex, but also hippocampus, striatum, and septum. In addition to vitamin K1, vitamin K2 and K3 also showed the same effect on cortical neurons. The effect of vitamins K1 and K2 was observed at concentrations from 10(-8) to 10(-6) M, and that of vitamin K3 was slightly detected at 10(-6) M. Furthermore, we examined the effect on the neurons from 16- and 21-day-old embryos, too. The activity of vitamin K1 was weaker toward the neurons from 21-day-old embryos compared with that toward 19-day-old ones, and was not recognized toward 16-day-old ones. These results suggest the potential role of the K vitamins on the maintenance of the survival of CNS neurons during the later stages of embryogenesis in vivo.