Research Article| Volume 283, ISSUE 1-2, P195-198, August 15, 2009

Brains of apolipoprotein E deficient mice fed vitamin E deficient diets show alteration in handling alpha tocopherol injected into the cerebral ventricles

  • Govind T. Vatassery
    Corresponding author. Research Service (151), V.A. Medical Center, Minneapolis, Minnesota 55417, USA. Tel.: +1 612 467 2910; fax: +1 612 725 2084.
    Research Service and the GRECC Program, V.A. Medical Center, Minneapolis, Minnesota, USA

    Department of Psychiatry and the Graduate Program in Neuroscience, University of Minnesota, Minneapolis 55455, USA
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  • W. Ed Smith
    Research Service and the GRECC Program, V.A. Medical Center, Minneapolis, Minnesota, USA
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  • Hung T. Quach
    Research Service and the GRECC Program, V.A. Medical Center, Minneapolis, Minnesota, USA
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      Abnormal function of apolipoprotein E (apoE) has been implicated in the incidence of some neurological disorders including dementia. Our recent experiments have shown that apoE deficiency alters the dynamics of alpha tocopherol (vitamin E) handling by brain. In the current investigation, we examined the uptake and retention of tritium-labeled alpha tocopherol that was injected into the lateral cerebral ventricles of apoE-deficient and wild type mice that were fed vitamin E-deficient diet. Eighteen weeks-old, male mice were fed vitamin E-deficient diets for 28 weeks. Labeled cholesterol was injected with the radioactive tocopherol and the cholesterol counts were used as internal standard. After an equilibration time of 48 h, radioactive alpha tocopherol levels in most brain regions were higher in apoE deficient animals when compared with the wild type. Along with our other data, this suggests that the clearance of vitamin E is slower in apoE-deficient brains. Nearly all of the injected alpha tocopherol was unchanged in the brains of both apoE-deficient and wild type animals (even with the additional dietary stress of vitamin E deficiency) suggesting low turnover rate of tocopherol in brain. The data strongly suggest that apoE is a key protein involved with the transport and/or retention of alpha tocopherol in brain.


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        • Corder E.H.
        • Saunders A.M.
        • Strittmatter W.J.
        • Schmechel D.E.
        • Gaskell P.C.
        • Small G.W.
        • et al.
        Gene dose of apolipoprotein E allele and the risk of Alzheimer's disease in late onset families.
        Science. 1993; 261: 921-923
        • Farrer L.A.
        • Cupples A.
        • Haines J.L.
        • Hyman B.
        • Kukull W.A.
        • Mayeux R.
        • et al.
        Effects of age, sex and ethnicity on the association between apolipoprotein E genotype and Alzheimer's disease.
        J Am Med Assoc. 1997; 278: 1349-1356
        • Mahley R.W.
        • Weisgraber K.H.
        • Huang Y.
        Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease.
        Proc Nat Acad Sci (USA). 2006; 103: 5644-5651
        • Pratico D.
        • Rokach J.
        • Tangirala R.K.
        Brains of aged apolipoprotein E-deficient mice have increased levels of F2-isoprostanes, in vivo markers of lipid peroxidation.
        J Neurochem. 1999; 73: 736-741
        • Shea T.B.
        • Rogers E.
        • Ashline D.
        • Ortiz D.
        • Sheu M.S.
        Apolipoprotein E deficiency promotes increased oxidative stress and compensatory increases in antioxidants in brain tissue.
        Free Rad Biol Med. 2002; 33: 1115-1120
        • Sano M.
        • Ernesto C.
        • Thomas R.G.
        • Klauber M.R.
        • Schafer K.
        • Grundman M.
        • et al.
        A controlled trial of selegiline, alpha tocopherol, or both as treatment for Alzheimer's disease.
        New Engl J Med. 1997; 336: 1216-1222
        • Vatassery G.T.
        • Lam C.
        • Smith W.E.
        • Quach H.T.
        Apolipoprotein E exerts selective and differential control over vitamin E concentrations in different areas of mammalian brain.
        J Neurosci Res. 2006; 84: 1335-1342
        • Vatassery G.T.
        • Quach H.T.
        • Smith W.E.
        • Santacruz K.S.
        • Roy S.
        Apolipoprotein e deficiency leads to altered brain uptake of alpha tocopherol injected into lateral cerebral ventricles.
        Biochim Biophys Acta. Jul 2007; 1772: 797-803
        • Reeves P.G.
        • Nielsen F.H.
        • Fahey Jr., G.C.
        AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition Ad Hoc committee on the reformulation of the AIN-76A rodent diet.
        J Nutr. 1993; 123: 1939-1951
        • Franklin K.J.
        • Paxinos G.
        The mouse brain in stereotaxic coordinates.
        Academic Press, New York1997
        • Glowinski J.
        • Iversen L.L.
        Regional studies of catecholamines in the rat brain.
        J Neurochem. 1966; 13: 655-669
        • Vatassery G.T.
        • Smith W.E.
        • Quach H.T.
        A liquid chromatographic method for the simultaneous determination of alpha tocopherol and tocopherolquinone in human red blood cells and other biological samples where tocopherol is easily oxidized during sample treatment.
        Anal Biochem. 1993; 214: 426-430
        • Markwell M.A.K.
        • Haas S.M.
        • Bieber L.L.
        • Tolbert N.E.
        A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples.
        Anal Biochem. 1978; 87: 206-210
        • Liu J.F.
        • Huang C.J.
        Dietary oxidized frying oil enhances tissue alpha-tocopherol depletion and radioisotope tracer excretion in vitamin E-deficient rats.
        J Nutr. Sep 1996; 126: 2227-2235
        • Vatassery G.T.
        • Quach H.T.
        • Smith W.E.
        • Kuskowski M.
        Deletion of apolipoprotein E gene modifies the rate of depletion of alpha tocopherol (vitamin E) from mice brains.
        Biochim Biophys Acta. Jun 2008; 1782: 414-420
        • Roheim P.S.
        • Carey M.
        • Forte T.
        • Vega G.L.
        Apolipoproteins in human cerebrospinal fluid.
        Proc Natl Acad Sci (USA). 1979; 76: 4646-4649
        • Mardones P.
        • Strobel P.
        • Miranda S.
        • Leighton F.
        • Quinones V.
        • Amigo L.
        • et al.
        Alpha tocopherol metabolism is abnormal in scavenger receptor class B type I (SR-B1)-deficient mice.
        J Nutr. 2002; 132: 443-449