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Nutritional Neurosciences

Menaquinone-4 Concentration Is Correlated with Sphingolipid Concentrations in Rat Brain¹

Isabelle Carrié, Jacques Portoukalian^*, Raffaela Vicaretti, Joseph Rochford, Stéphanie Potvin and Guylaine Ferland²

Département de Nutrition, Université de Montréal, H3C 3J7 Montréal, Canada; ^* INSERM U346, Dermatologie, Hôpital Edouard Herriot, Lyon, France and Douglas Hospital Research Center, Department of Psychiatry, McGill University, Montréal, Canada

²To whom correspondence should be addressed. E-mail: Guylaine.Ferland{at}umontreal.ca.

Studies with animals support a role for vitamin K (VK) in the biosynthesis of sphingolipids, a class of complex lipids present in high concentrations in the brain. In mice and rats, VK deficiency decreases levels of brain sulfatides and causes behavioral alterations. In light of its heterogeneity and to better understand the role of VK in the brain, we characterized the distribution of the two main VK vitamers, phylloquinone (K₁) and menaquinone-4 (MK-4), in nine distinct brain regions. Weaning female Sprague-Dawley rats (n = 5/dietary group) were fed diets containing either low (L, 80 µg/kg diet), adequate (A, 500 µg/kg diet) or high (H, 2000 µg/kg diet) levels of K₁ for 6 mo. The main form of VK in the brain was MK-4, and it was present in significantly higher concentrations in myelinated regions (the pons medulla and midbrain) than in nonmyelinated regions. Both regional K₁ and MK-4 increased with K₁ intake (P < 0.05). Sphingolipid distribution varied across brain regions (P < 0.001) but was not affected by K₁ intake. In the L and A groups but not the H group, brain MK-4 concentration was positively correlated with the concentrations of sulfatides (L, r = 0.518; A, r = 0.479) and sphingomyelin (L, r = 0.515; A, r = 0.426), and negatively correlated with ganglioside concentration (L, r = -0.398); A, r = -0.353). Sphingolipids are involved in major cellular events such as cell proliferation, differentiation and survival. The strong associations reported here between brain MK-4 and sphingomyelin, sulfatides and gangliosides suggest that this vitamer may play an important role in the brain.

KEY WORDS: • vitamin K • phylloquinone • menaquinone-4 • sphingolipids • brain • rats

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				S. L. Booth, J. W. Peterson, D. Smith, M. K. Shea, J. Chamberland, and N. Crivello Age and Dietary Form of Vitamin K Affect Menaquinone-4 Concentrations in Male Fischer 344 Rats J. Nutr., March 1, 2008; 138(3): 492 - 496. [Abstract] [Full Text] [PDF]