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. 2010 Nov;21(11):1083-8.
doi: 10.1016/j.jnutbio.2009.09.005. Epub 2010 Jan 25.

Age- And Brain Region-Specific Effects of Dietary Vitamin K on Myelin Sulfatides

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Age- And Brain Region-Specific Effects of Dietary Vitamin K on Myelin Sulfatides

Natalia A Crivello et al. J Nutr Biochem. .
Free PMC article

Abstract

Dysregulation of myelin sulfatides is a risk factor for cognitive decline with age. Vitamin K is present in high concentrations in the brain and has been implicated in the regulation of sulfatide metabolism. Our objective was to investigate the age-related interrelation between dietary vitamin K and sulfatides in myelin fractions isolated from the brain regions of Fischer 344 male rats fed one of two dietary forms of vitamin K: phylloquinone or its hydrogenated form, 2',3'-dihydrophylloquinone (dK), for 28 days. Both dietary forms of vitamin K were converted to menaquinone-4 (MK-4) in the brain. The efficiency of dietary dK conversion to MK-4 compared to dietary phylloquinone was lower in the striatum and cortex, and was similar to that in the hippocampus. There were significant positive correlations between sulfatides and MK-4 in the hippocampus (phylloquinone-supplemented diet, 12 and 24 months; dK-supplemented diet, 12 months) and cortex (phylloquinone-supplemented diet, 12 and 24 months). No significant correlations were observed in the striatum. Furthermore, sulfatides in the hippocampus were significantly positively correlated with MK-4 in serum. This is the first attempt to establish and characterize a novel animal model that exploits the inability of dietary dK to convert to brain MK-4 to study the dietary effects of vitamin K on brain sulfatide in brain regions controlling motor and cognitive functions. Our findings suggest that this animal model may be useful for investigation of the effect of the dietary vitamin K on sulfatide metabolism, myelin structure and behavior functions.

Figures

Figure 1
Figure 1
Twenty 2-month-old (young), twenty 12-month-old (adult) and twenty 24-month-old (old) male Fischer rats were obtained from the National Institutes of Aging (Harlan Sprague Dawley, Indianapolis, IN). Rats were maintained on experimental diets for 28 days. Vitamin K and sulfatide content was determined in myelin fraction isolated from brain regions as described in Material and methods.
Figure 2
Figure 2
(A, B, C). The association between MK-4 and sulfatides in myelin fractions isolated from the hippocampus (A), striatum (B), and cortex (C) of adult (12 mo) and old (24 mo) rats exposed to dietary phylloquinone (K1 diet) and dihydrophylloquinone (dK diet). Data points are concentrations of MK-4 and sulfatides from the hippocampus (n per K1 gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-5), striatum (n per K1gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-5), and cortex (n per K1 gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-4) of rats fed with phylloquinone (K1) or dihydrophylloquinone (dK) diets. Data points collected from two rats (12mo, K1 diet and 24mo, dK diet) were excluded from the analyses as outliers. Three cortical samples from the dK dietary group (two, 12mo and one, 24mo) did not contain a sufficient amount of sample for the assessment of MK-4 (i.e., values were below the minimum detectable concentrations of 0.05nmol/kg tissue).
Figure 2
Figure 2
(A, B, C). The association between MK-4 and sulfatides in myelin fractions isolated from the hippocampus (A), striatum (B), and cortex (C) of adult (12 mo) and old (24 mo) rats exposed to dietary phylloquinone (K1 diet) and dihydrophylloquinone (dK diet). Data points are concentrations of MK-4 and sulfatides from the hippocampus (n per K1 gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-5), striatum (n per K1gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-5), and cortex (n per K1 gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-4) of rats fed with phylloquinone (K1) or dihydrophylloquinone (dK) diets. Data points collected from two rats (12mo, K1 diet and 24mo, dK diet) were excluded from the analyses as outliers. Three cortical samples from the dK dietary group (two, 12mo and one, 24mo) did not contain a sufficient amount of sample for the assessment of MK-4 (i.e., values were below the minimum detectable concentrations of 0.05nmol/kg tissue).
Figure 2
Figure 2
(A, B, C). The association between MK-4 and sulfatides in myelin fractions isolated from the hippocampus (A), striatum (B), and cortex (C) of adult (12 mo) and old (24 mo) rats exposed to dietary phylloquinone (K1 diet) and dihydrophylloquinone (dK diet). Data points are concentrations of MK-4 and sulfatides from the hippocampus (n per K1 gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-5), striatum (n per K1gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-5), and cortex (n per K1 gr.: 12mo-9; 24mo-8; n per dK gr.: 12mo-10; 24mo-4) of rats fed with phylloquinone (K1) or dihydrophylloquinone (dK) diets. Data points collected from two rats (12mo, K1 diet and 24mo, dK diet) were excluded from the analyses as outliers. Three cortical samples from the dK dietary group (two, 12mo and one, 24mo) did not contain a sufficient amount of sample for the assessment of MK-4 (i.e., values were below the minimum detectable concentrations of 0.05nmol/kg tissue).
Figure 3
Figure 3
Potential mechanism of conversion of the dietary forms of vitamin K to menaquinone-4.

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