Nutrition and Central Nervous System

  • Silvina Monica Alvarez
  • Nidia N. Gomez
  • Lorena Navigatore Fonzo
  • Emilse S. Sanchez
  • María Sofía Giménez


Clinical studies have revealed that depression is accompanied by impaired brain function and cognitive performances or neurodegenerative processes. Moreover, accumulation of oxidative damage has been implicated in aging and various neurological disorders. This chapter aims to integrate the current knowledge on the relation between brain and diverse alterations in nutrition. The mammalian brain is a lipid-rich organ, where lipids content in gray matter is 36–40% lipid. However, the regulation of cholesterol transport from astrocytes to neurons still remains unclear, among other things. In addition to that, micronutrient status can affect cognitive function at all ages. Vitamin deficiency could influence memory function, and might contribute to cognitive impairment and dementia.

Deficiency of vitamin A, folate, vitamins B6, B12, and minerals such as Fe and Zn are associated with prevalence of depressive symptoms according to several epidemiological studies. Experimental evidence suggests that resveratrol, vitamins A, C, E, D and folate may block oxidative stress and promote clearance of Aβ peptides. An adequate intake of fruit, nuts, vegetables, cereals, legumes, or fish can prevent the depletion. High dietary intake of saturated fat and low intake of vegetables may be associated with increased risk of Alzheimer’s disease. Supplementation of diets with omega-3 has been shown to have positive effects on cognitive function. The biochemical and molecular mechanism of these alterations of normal brain function has been described. Future studies should also examine how DNA repair deficiency occurs and affects the nervous system, because this could provide a rational basis for therapies in neurodegenerative diseases.


Central nervous system Vitamins Alzheimer’s disease Dementia Zinc Fatty acids Glucose Insulin 


  1. 1.
    Gomez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9:568–78.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Simons M, Trajkovic K. Neuron–glia communication in the control of oligodendrocyte function and myelin biogenesis. J Cell Sci. 2006;119:4381–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Kendler KS, Gardner CO, Prescott CA. Toward a comprehensive developmental model for major depression in women. Am J Psychiatry. 2002;159:1133–45.PubMedCrossRefGoogle Scholar
  4. 4.
    Morgan KD, Dazzan P, Orr KG, Hutchinson G, Chitnis X, Suckling J, Lythgoe D, Pollock SJ, Rossell S, Shapleske J, Fearon P, Morgan C, David A, McGuire PK, Jones PB, Leff J, Murray RM. Grey matter abnormalities in first-episode schizophrenia and affective psychosis. B J Psych. 2007;191:s111–6.CrossRefGoogle Scholar
  5. 5.
    Moore JK, Perazzo LM, Braun A. Time course of axonal myelination in the human brainstem auditory pathway. Hear Res. 1995;87:21–31.PubMedCrossRefGoogle Scholar
  6. 6.
    Miller SL, Klurfeld DM, Loftus B, Kritchevsky D. Effect of essential fatty acid deficiency on myelin proteins. Lipids. 1984;19:478–80.PubMedCrossRefGoogle Scholar
  7. 7.
    McKenna MC, Campagnoni AT. Effect of pre- and postnatal essential fatty acid deficiency on brain development and myelination. J Nutr. 1979;109:​1195–204.PubMedGoogle Scholar
  8. 8.
    Silvestroff L, Franco PG, Pasquini JM. Neural and oligodendrocyte progenitor cells: transferrin effects on cell proliferation. ASN Neuro. 2013;5(1):e00107. doi: 10.1042/AN20120075.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Kwik-Uribe CL, Gietzen D, German JB, Golub MS, Keen CL. Chronic marginal iron intakes during early development in mice result in persistent changes in dopamine metabolism and myelin composition. J Nutr. 2000;130:2821–30.PubMedGoogle Scholar
  10. 10.
    Chen MH, Su TP, Chen YS, Hsu JW, Huang KL, Chang WH, Chen TJ, Bai YM. Association between psychiatric disorders and iron deficiency anemia among children and adolescents: a nationwide population-based study. BMC Psychiatry. 2013;13:161.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Nielsen PR, Meyer U, Mortensen PB. Individual and combined effects of maternal anemia and prenatal infection on risk for schizophrenia in offspring. Schizophr Res. 2016;172(1–3):35–40.PubMedCrossRefGoogle Scholar
  12. 12.
    de Escobar GM, Obregon MJ, del Rey FE. Iodine deficiency and brain development in the first half of pregnancy. Public Health Nutr. 2007;10:​1554–70.PubMedCrossRefGoogle Scholar
  13. 13.
    Dussault JH, Ruel J. Thyroid hormones and brain development. Annu Rev Physiol. 1987;49:321–34.PubMedCrossRefGoogle Scholar
  14. 14.
    Kanık-Yuksek S, Aycan Z, Oner O. Evaluation of iodine deficiency in children with attention-deficit/hyperactivity disorder. J Clin Res Pediatr Endicrinol. 2016;8(1):61–6.CrossRefGoogle Scholar
  15. 15.
    Sanchez ES, Bigbee JW, Fobbs W, Robinson SE, Sato-Bigbee C. Opioid addiction and pregnancy: perinatal exposure to buprenorphine affects myelination in the developing brain. Glia. 2009;56(9):1017–27.CrossRefGoogle Scholar
  16. 16.
    Hsu DT, Sanford BJ, Meyers KK, Love TM, Hazlett KE, Walker SJ, Mickey BJ, Koeppe RA, Langenecker SA, Zubieta JK. It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder. Mol Psychiatry. 2015;20(2):193–200.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Aston C, Jiang L, Sokolov BP. Microarray analysis of postmortem temporal cortex from patients with schizophrenia. J Neurosci Res. 2004;77(6):858–66.PubMedCrossRefGoogle Scholar
  18. 18.
    Barandas R, Landgraf D, McCarthy MJ, Welsh DK. Circadian clocks as modulators of metabolic comorbidity in psychiatric disorders. Curr Psychia Rep. 2015;17(12):98. doi: 10.1007/s11920-015-0637-2.CrossRefGoogle Scholar
  19. 19.
    Mergenthaler P, Lindauer U, Dienel GA, Meisel A. Sugar for the brain — the role of glucose in physiological and pathological brain function. Trends Neurosci. 2013;36(10):587–97.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Magistretti PJ, Sorg O, Yu N, Martin JL, Pellerin L. Neurotransmitter regulates energy metabolism in astrocytes: implications for the metabolic trafficking between neural cells. Dev Neurosci. 1993;15:​306–12.PubMedCrossRefGoogle Scholar
  21. 21.
    Brown AM, Baltan Tekkök S, Ransom BR. Energy transfer from astrocytes to axons: the role of CNS glycogen. Neurochem Int. 2004;45:529–36.PubMedCrossRefGoogle Scholar
  22. 22.
    Vilchez D, Ros S, Cifuentes D, Pujadas L, Valles J, Garcia-Fojeda B, Criado-Garcia O, Fernandez-Sanchez E, Medraño-Fernández I, Dominguez J, Garcia-Rocha M, Soriano E, Rodriguez de Cordoba S, Guinovart JJ. Mechanism suppressing glycogen synthesis in neurons and its demise in progressive myoclonus epilepsy. Nat Neurosci. 2007;10:1407–13.PubMedCrossRefGoogle Scholar
  23. 23.
    Hertz L, Gibbs ME. What learning in day-old chickens can teach a neurochemist: focus on astrocyte metabolism. J Neurochem. 2009;109(s1):10–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM. Astrocyte–neuron lactate transport is required for long term memory formation. Cell. 2011;144:810–23.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Garcia-Nogales P, Almeida A, Bolaños JP. Peroxynitrite protects neurons against nitric oxide-mediated apoptosis. A key role for glucose-6-phosphate dehydrogenase activity in neuroprotection. JBC. 2003;278:864–74.CrossRefGoogle Scholar
  26. 26.
    Ben-Yoseph O, Boxer PA, Ross BD. Noninvasive assessment of the relative roles of cerebral antioxidant enzymes by quantitation of pentose phosphate pathway activity. Neurochem Res. 1996;21:1005–12.PubMedCrossRefGoogle Scholar
  27. 27.
    Lovatt D, Sonnewald U, Waagepetersen HS, Schousboe A, He W, Lin JH, Han X, Takano T, Wang S, Sim FJ, Goldman SA, Nedergaard M. The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. J Neurosci. 2007;27:12255–66.PubMedCrossRefGoogle Scholar
  28. 28.
    Cahoy JD, Emery B, Kaushal A, Foo LC, Zamanian JL, Christopherson KS, Xing Y, Lubischer JL, Kireg PA, Krupenko SA, Thompson WJ, Barres BA. A transcriptome database for astrocytes, neurons and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci. 2008;28:264–78.PubMedCrossRefGoogle Scholar
  29. 29.
    Banting FG, Best CH. The internal secretion of the pancreas. J Lab Clin Med. 1922;7:251–66.Google Scholar
  30. 30.
    Margolis RU, Altszuler N. Insulin in the cerebrospinal fluid. Nature. 1967;215:1375–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Banks WA, Owen JB, Erickson MA. Insulin in the brain: there and back again. Pharmacol Ther. 2012;136:82–93.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Havrankova J, Schmechel D, Roth J, Brownstein M. Identification of insulin in rat brain. Proc Natl Acad Sci U S A. 1978;75:5737–41.PubMedPubMedCentralCrossRefGoogle Scholar
  33. 33.
    Dorn A, Bernstein HG, Rinne A, Ziegler M, Hahn HJ, Ansorge S. Insulin- and glucagonlike peptides in the brain. Anat Rec. 1983;207:69–77.PubMedCrossRefGoogle Scholar
  34. 34.
    Duarte AI, Proenca T, Oliveira CR, Santos MS, Rego AC. Insulin restores metabolic function in cultured cortical neurons subjected to oxidative srtress. Diabetes. 2006;55:2863–70.PubMedCrossRefGoogle Scholar
  35. 35.
    Bosco D, Fava A, Plastino M, Montalcini T, Pujia A. Possible implications of insulin resistance and glucose metabolism in Alzheimer s disease pathogenesis. J Cell Mol Med. 2011;17:1807–21.CrossRefGoogle Scholar
  36. 36.
    Tolpannen AM, Lavikainen P, Solomon A, Kivipelto M, Uusitupa M, Soininen H, Hartikainen S. History of medically treated diabetes and risk of Alzheimer disease in a nationwide case-control study. Diabetes Care. 2013;36:2015–9.CrossRefGoogle Scholar
  37. 37.
    Blazquez E, Velasquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. Insulin in the brain: its pathophisiological implications for states related with central insulin resistance, type 2 diabetes and Alzheimer s disease. Front Endocrinol (Lausanne). 2014;5:161. doi: 10.3389/fendo.2014.00161.Google Scholar
  38. 38.
    O’Brien JS, Sampson EL. Lipid composition of normal human brain: gray matter, white matter, and myelin. J Lipid Res. 1965;6:537–44.PubMedGoogle Scholar
  39. 39.
    Salem Jr N, Kim H-Y, Yergey JA. Docosahexaenoic acid: membrane function and metabolism. In: Simopoulos AP, Kiter RR, Martin RE, editors. Health effects of polyunsaturated fatty acids in seafoods. New York: Academic Press; 1986. p. 263–317.CrossRefGoogle Scholar
  40. 40.
    Ikemoto A, Kobayashi T, Watanabe S, Okuyama H. Membrane fatty acid modifications of PC12 cells by arachidonate or docosahexaenoate affect neurite outgrowth but not norepinephrine release. Neurochem Res. 1997;22(6):671–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Bourre JM. Roles of unsaturated fatty acids (especially omega-3 fatty acids) in the brain at various ages and during aging. J Nutr Health Aging. 2004;8:163–74.PubMedGoogle Scholar
  42. 42.
    Cook HW. In vitro formation of polyunsaturated fatty acids by desaturation in rat brain: some properties of the enzyme in developing brain and comparison with liver. J Neurochem. 1978;30:1327–34.PubMedCrossRefGoogle Scholar
  43. 43.
    Purvis M, Clandinin MT, Hacker RR. Chain elongation–desaturation of linoleic acid during the development of the pig: implications for the supply of polyenoic fatty acids to the developing brain. Comp Biochem Physiol. 1983;75B:199–204.Google Scholar
  44. 44.
    Delaš I, Popovic M, Petrovic T, Delaš F, Ivankovic D. Changes in the fatty acid composition of brain and liver phospholipids from rats fed fat-free diet. Food Technol Biotechnol. 2008;3:278–85.Google Scholar
  45. 45.
    Bourre J-M, Durand G, Pascal G, Youyou A. Brain cell and tissuerecovery in rats made deficient in n-3 fatty acids by alteration of dietary fat. J Nutr. 1989;119:15–22.PubMedGoogle Scholar
  46. 46.
    Salem N, Moriguchi T, Greiner RS, et al. Alterations in brain function after loss of docosahexaenoate due to dietary restriction of n-3 fatty acids. J Mol Neurosci. 2001;16:299–307.PubMedCrossRefGoogle Scholar
  47. 47.
    Bourre JM, Francois M, Youyou A, Dumont O, Piciotti M, Pascal G. The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr. 1989b;119:1880–92.PubMedGoogle Scholar
  48. 48.
    Bourre JM, Dumont O, Pascal G, Durand G. Dietary alpha linolenic acid at 1.3 g/kg maintains maximal docosahexaenoic acid concentration in brain, heart and liver of adult rats. J Nutr. 1993;123:1313–9.PubMedGoogle Scholar
  49. 49.
    Uauy R, Mena P, Rojas C. Essential fatty acids in early life: structural and functional role. Proc Nutr Soc. 2000;59:3–15.PubMedCrossRefGoogle Scholar
  50. 50.
    Morris MC, Tangney CC. Dietary fat composition and dementia risk. Neurobiol Aging. 2014;35(suppl 2):S59–64.PubMedCrossRefGoogle Scholar
  51. 51.
    Appleton KM, Rogers PJ, Ness AR. Updated systematic review and meta-analysis of the effects of n-3 long-chain polyunsaturated fatty acids on depressed mood. Am J Clin Nutr. 2010;91:​757–70.PubMedCrossRefGoogle Scholar
  52. 52.
    Ferreira CF, Bernardi JR, da Silva DC, de Sa C-PN, de Souza MC, Krolow R, Weis SN, Pettenuzzo L, Kapczinski F, Silveira PP, Dalmaz O. Mitochondrial and oxidative stress aspects in hippocampus of rats submitted to dietary n-3 polyunsaturated fatty acid deficiency after exposure to early stress. Neurochem Res. 2015;40:1870–81.PubMedCrossRefGoogle Scholar
  53. 53.
    Grosso G, Galvano F, Marventano S, Malaquarnera M, Bucolo C, Drago F, Caraci F. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxidative Med Cell Longev. 2014;2014:313570. doi: 10.1155/2014/313570.CrossRefGoogle Scholar
  54. 54.
    Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition. 2015;31:781–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Perica MM, Delas I. Essential fatty acids and psychiatric disorders. Nutr Clin Pract. 2011;26:409–25.PubMedCrossRefGoogle Scholar
  56. 56.
    Soderberg M, Edlund C, Kristensson K, Dallner G. Fatty acid composition of brain phospholipids in aging and in Alzheimer’s disease. Lipids. 1991;26:​421–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Plourde M, Fortier M, Vandal M, Tremblay-Mercier J, Freemantle E, Begin M, Pifferi F, Cunnane SC. Unresolved issues in the link between docosahexaenoic acid and Alzheimer’s disease. Prostaglandins Leukot Essent Fat Acids. 2007;77:301–8.CrossRefGoogle Scholar
  58. 58.
    Horrocks LA, Farooqui AA. Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function. Prostaglandins Leukot Essent Fat Acids. 2004;70:361–72.CrossRefGoogle Scholar
  59. 59.
    Uauy R, Hoffman DR, Peirano P, Birch DG, Birch EE. Essential fatty acids in visual and brain development. Lipids. 2001;36:885–95.PubMedCrossRefGoogle Scholar
  60. 60.
    Lane RM, Farlow MR. Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer’s disease. J Lipid Res. 2005;46:949–68.PubMedCrossRefGoogle Scholar
  61. 61.
    Fan YY, McMurray DN, Ly LH, Chapkin RS. Dietary (n-3) polyunsaturated fatty acids remodel mouse T-cell lipid rafts. J Nutr. 2003;133:1913–2190.PubMedGoogle Scholar
  62. 62.
    Ma DW, Seo J, Switzer KC, Fan YY, McMurray DN, Lupton JR, Chapkin RS. n-3 PUFA and membrane microdomains: a new frontier in bioactive lipid research. J Nutr Biochem. 2004;15:700–6.PubMedCrossRefGoogle Scholar
  63. 63.
    Brown DA, London E. Structure and function of sphingolipid- and cholesterol-rich membrane rafts. J Biol Chem. 2000;275:17221–4.PubMedCrossRefGoogle Scholar
  64. 64.
    Michel V, Bakovic M. Lipid rafts in health and disease. Biol Cell. 2007;99:129–40.PubMedCrossRefGoogle Scholar
  65. 65.
    Pfrieger FW. Cholesterol homeostasis and function in neurons of the central nervous system. Cell Mol Life Sci. 2003;60:1158–71.PubMedCrossRefGoogle Scholar
  66. 66.
    Björkhem I, Lütjohann D, Diczfalusy U, Stahle L, Ahiborg G, Wahren J. Cholesterol homeostasis in human brain: turnover of 24S-hydroxycholesterol and evidence for a cerebral origin of most of this oxysterol in the circulation. J Lipid Res. 1998;39:​1594–600.PubMedGoogle Scholar
  67. 67.
    Segatto M, Di Giovanni A, Marino M, Pallottini V. Analysis of the protein network of cholesterol homeostasis in different brain regions: an age and sex dependent perspective. J Cell Physiol. 2013;228:​1561–7.PubMedCrossRefGoogle Scholar
  68. 68.
    Swanson LW, Simmons DM, Hofmann SL, Goldstein JL, Brown MS. Localization of mRNA for low density lipoprotein receptor and a cholesterol synthetic enzyme in rabbit nervous system by in situ hybridization. Proc Natl Acad Sci U S A. 1988;85:9821–5.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Mauch DH, Nägler K, Schumacher S, Göritz C, Müller EC, Otto A, et al. CNS synaptogenesis promoted by glia-derived cholesterol. Science. 2001;294:1354–7.PubMedCrossRefGoogle Scholar
  70. 70.
    DeBose-Boyd RA. Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG coA reductase. Cell Res. 2008;18:609–21.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 1997;89:331–40.PubMedCrossRefGoogle Scholar
  72. 72.
    Wang Y, Muneton S, Sjövall J, Jovanovic JN, Griffiths WJ. The effect of 24S-hydroxycholesterol on cholesterol homeostasis in neurons quantitative changes to the cortical neuron proteome. J Proteome Res. 2008;7:1606–14.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 73.
    Popescu BF, Nichol H. Mapping brain metals to evaluate therapies for neuro-degenerative disease. CNS Neurosci Ther. 2011;17(4):256–68.PubMedCrossRefGoogle Scholar
  74. 74.
    Frederickson CJ, Suh SW, Silva D, Thompson RB. Importance of zinc in the central nervous system: the zinc-containing neuron. J. Nutrition. 2000;130:1471S–81S.Google Scholar
  75. 75.
    Bertoni-Freddari C, Mocchegiani E, Malavolta M, Casoli T, Di Stefano G, Fattoretti P. Synaptic and mitochondria physiopathologic changes in the aging nervous system and the role of zinc ion homeostasis. Mech Ageing Dev. 2006;127:590–6.PubMedCrossRefGoogle Scholar
  76. 76.
    Caulfield LE, Zavaleta N, Shankar AH, Merialdi M. Potential contribution of maternal zinc supplementation during pregnancy to maternal and child survival. Am J Clin Nutr. 1998;68(2 Suppl):​499S–508S.PubMedGoogle Scholar
  77. 77.
    Cunnane SC, Yang J. Zinc deficiency impairs whole-body accumulation of polyunsaturates and increases the utilization of [1-14C] linoleate for de novo lipid synthesis in pregnant rats. Can J Physiol Pharmacol. 1995;73:1246–52.PubMedCrossRefGoogle Scholar
  78. 78.
    Golub M, Keen C, Gershwin M, Hendrickx A. Developmental zinc deficiency and behaviour. J Nutr. 1995;125:2263S–71S.PubMedGoogle Scholar
  79. 79.
    Tamura T, Goldenberg RL, Ramey SL, Nelson KG, Chapman VR. Effect of zinc supplementation of pregnant women on the mental and psychomotor development of their children at 5 years of age. Am J Clin Nutr. 2003;77:1512–6.PubMedGoogle Scholar
  80. 80.
    Perez-Rosello T, Anderson CT, Schopfer FJ, Zhao Y, Gilad D, Salvatore SR, Freeman BA, Hershfinkel M, Aizenman E, Tzounopoulos T. Synaptic Zn2+ inhibits neurotransmitter release by promoting endocannabinoid synthesis. J Neurosci. 2013;33(22):​9259–72.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Bhatnagar S, Taneja S. Zinc and cognitive development. Br J Nutr. 2001;85:S139–S45.PubMedCrossRefGoogle Scholar
  82. 82.
    Chou H, Chien C, Huang H, Lu K. Effects of zinc deficiency on the vallatepapillae and taste buds in rats. J Formos Med Assoc. 2001;100:326–35.PubMedGoogle Scholar
  83. 83.
    Shah D, Sachdev HP. Zinc deficiency in pregnancy and fetal outcome. Nutr Rev. 2006;64(1):15–30.PubMedCrossRefGoogle Scholar
  84. 84.
    Piechal A, Blecharz-Klin K, Pyrzanowska J, Widy-Tyszkiewicz E. Maternal zinc supplementation improves spatial memory in rat pups. Biol Trace Elem Res. 2012;147:299–308.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Jayasooriya AP, Ackland ML, Mathai ML, Sinclair AJ, Weisinger HS, Weisinger RS, Halver JE, Kitajka K, Puskas LG. Perinatal omega-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood. Proc Natl Acad Sci U S A. 2005;102:7133–8.PubMedPubMedCentralCrossRefGoogle Scholar
  86. 86.
    Yu X, Chen W, Wei Z, Ren T, Yang X, Yu X. Effects of maternal mild zinc deficiency and different ways of zinc supplementation for offspring on learning and memory. Food Nutr Res. 2016;60:29467. PubMedCrossRefGoogle Scholar
  87. 87.
    Contestabile A, Peña-Altamira E, Virgili M, Monti B. Zinc supplementation in rats impairs hippocampal dependent memory consolidation and dampens post-traumatic recollection of stressful event. Eur Neuropsychopharmacol. 2016;26(6):1070–82. doi: 10.1016/j.euroneuro.2015.12.041. pii: S0924-977X(15)00431-9PubMedCrossRefGoogle Scholar
  88. 88.
    Pozzi D, Lignani G, Ferrea E, Contestabile A, Paonessa F, D’Alessandro R, Lippiello P, Boido D, Fassio A, Meldolesi J, Valtorta F, Benfenati F, Baldelli P. REST/NRSF-mediated intrinsic homeostasis protects neuronal networks from hyperexcitability. EMBO J. 2013;32:2994–3007.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Association; 2013.CrossRefGoogle Scholar
  90. 90.
    Jicha G, Carr S. Conceptual evolution in Alzheimer’s disease: implications for understanding the clinical phenotype of progressive neurodegenerative disease. J Alzheimers Dis. 2010;19(1):253–72.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Pimplikar S, Nixon R, Robakis N, Shen J, Tsai L. Amyloid-independent mechanisms in Alzheimer’s disease pathogenesis. J Neurosci. 2010;30:14946–54.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Alzheimer’s Association Report. Alzheimer’s disease facts and figures Alzheimer’s Association. Alzheimers Dement. 2015;11:332–84.CrossRefGoogle Scholar
  93. 93.
    Daviglus M, Bell C, Berrettini W. National institutes of health state-of-the-science conference statement: preventing Alzheimer disease and cognitive decline. Ann Intern Med. 2010;153(3):176–81.PubMedCrossRefGoogle Scholar
  94. 94.
    Larson E, Yaffe K, Langa K. New insights into the dementia epidemic. N Engl J Med. 2013;​369(24):2275–7.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Devore E, Grodstein F, van Rooij F, Hofman A, Stampfer M, Witteman J, Breteler M. Dietary antioxidants and long-term risk of dementia. Arch Neurol. 2010;67(7):819–25.PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    Gillette-Guyonnet S, Secher M, Vellas B. Nutrition and neurodegeneration: epidemiological evidence and challenges for future research. Br J Clin Pharmacol. 2013;75(3):738–55.PubMedPubMedCentralCrossRefGoogle Scholar
  97. 97.
    Haan M, Miller J, Aiello A, Whitmer R, Jagust W, Mungas D, Allen L, Green R. Homocysteine, B vitamins, and the incidence of dementia and cognitive impairment: results from the Sacramento Area Latino Study on Aging. Am J Clin Nutr. 2007;​85(2):511–7.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Slinin Y, Paudel M, Taylor B, Fink H, Ishani A, Canales M, Yaffe K, Barrett-Connor E, Orwoll E, Shikany J, Leblanc E, Cauley J, Ensrud K. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men. Neurology. 2010;74(1):33–41.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Malouf R, Grimley E. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008;4:CD004514.Google Scholar
  100. 100.
    Mooijaart S, Gussqekloo J, Frolich M, Jolles J, Stott DJ, Westendorp RGJ, de Craen A. Homocysteine, vitamin B-12, and folic acid and the risk of cognitive decline in old age: the Leiden 85-Plus study. Am J Clin Nutr. 2005;82:866–71.PubMedGoogle Scholar
  101. 101.
    Ueland P, Hustad S, Schneede J, Refsum H, Vollset S. Biological and clinical implications of the MTHFR C677T polymorphism. Trends Pharmacol Sci. 2001;22:195–201.PubMedCrossRefGoogle Scholar
  102. 102.
    Coppedè F. One-carbon metabolism and Alzheimer’s disease: focus on epigenetics. Curr Genet. 2010;11:246–60.CrossRefGoogle Scholar
  103. 103.
    Aisen P, Egelko S, Andrews H, Diaz-Arrastia R, Weiner M, DeCarli C, Jagust W, Miller J, Green R, Bell K, Sano M. A pilot study of vitamins to lower plasma homocysteine levels in Alzheimer disease. Am J Geriatr Psychiatry. 2003;11:246–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Faux N, Ellis K, Porter L, Fowler C, Laws S, Martins R, Pertile K, Rembach A, Rowe C, Rumble R, Szoeke C, Taddei K, Taddei T, Trounson B, Villemagne V, Ward V, Ames D, Masters CL, Bush AI. Homocysteine, vitamin B12, and folic acid levels in Alzheimer’s disease, mild cognitive impairment, and healthy elderly: baseline characteristics in subjects of the Australian Imaging Biomarker Lifestyle study. J Alzheimers Dis. 2011;27:909–22.PubMedGoogle Scholar
  105. 105.
    Shea T, Lyons-Weiler J, Rogers E. Homocysteine, folate deprivation and Alzheimer neuropathology. J Alzheimers Dis. 2002;4:261–7.PubMedCrossRefGoogle Scholar
  106. 106.
    Aisen P, Schneider L, Sano M, Diaz-Arrastia R, van Dyck C, Weiner M, Bottiglieri T, Jin S, Stokes K, Thomas R, Thal L. High-dose B vitamin supplementation and cognitive decline in Alzheimer disease: a randomized controlled trial. JAMA. 2008;300:​1774–83.PubMedPubMedCentralCrossRefGoogle Scholar
  107. 107.
    Smith A, Smith S, de Jager C, Whitbread P, Johnston C, Agacinski G, Oulhaj A, Bradley K, Jacoby R, Refsum H. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One. 2010;5(9):e12244. doi: 10.1371/journal.pone.0012244.PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Gubandru M, Margina D, Tsitsimpikou C, Goutzourelas N, Tsarouhas K, Ilie M, Tsatsakis A, Kouretas D. Alzheimer’s disease treated patients showed different patterns for oxidative stress and inflammation markers. Food Chem Toxicol. 2013;​61:209–14.PubMedCrossRefGoogle Scholar
  109. 109.
    Mariani E, Polidori M, Cherubini A, Mecocci P. Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. J Chromatogr B Anal Technol Biomed Life Sci. 2005;827:65–75.CrossRefGoogle Scholar
  110. 110.
    Heo J, Hyon-Lee LK. The possible role of antioxidant vitamin C in Alzheimer’s disease treatment and prevention. Am J Alzheimers Dis Other Demen. 2013;28:120–5.PubMedCrossRefGoogle Scholar
  111. 111.
    Jiang Q. Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy. Free Radic Biol Med. 2014;72:76–90.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Niki E. Role of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in vivo evidence. Free Radic Biol Med. 2014;66:3–12.PubMedCrossRefGoogle Scholar
  113. 113.
    Rigotti A. Absorption, transport, and tissue delivery of vitamin E. Mol Asp Med. 2007;28:423–36.CrossRefGoogle Scholar
  114. 114.
    Fukui K, Nakamura K, Shirai M, Hirano A, Takatsu H, Urano S. Long-term vitamin E-deficient mice exhibit cognitive dysfunction via elevation of brain oxidation. J Nutr Sci Vitaminol (Tokyo). 2015;61:​362–8.CrossRefGoogle Scholar
  115. 115.
    Niki E, Traber MG. A history of vitamin E. Ann Nutr Metab. 2012;61:207–12.PubMedCrossRefGoogle Scholar
  116. 116.
    Dysken M, Sano M, Asthana S, Vertrees J, Pallaki M, Llorente M, Love S, Schellenberg G, McCarten J, Malphurs J, Prieto S, Chen P, Loreck D, Trapp G, Bakshi R, Mintzer J, Heidebrink J, Vidal-Cardona A, Arroyo L, Cruz A, Zachariah S, Kowall N, Chopra M, Craft S, Thielke S, Turvey C, Woodman C, Monnell K, Gordon TJ, Segal Y, Peduzzi P, Guarino P. Effect of vitamin E and memantine on functional decline in Alzheimer disease: the TEAM-AD VA cooperative randomized trial. JAMA. 2014;311:​33–44.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 117.
    Mangialasche F, Xu W, Kivipelto M, Costanzi E, Ercolani S, Pigliautile M, Cecchetti R, Baglioni M, Simmons A, Soininen H, Tsolaki M, Kloszewska I, Vellas B, Lovestone S, Mecocci P, AddNeuroMed Consortium. Tocopherols and tocotrienols plasma levels are associated with cognitive impairment. Neurobiol Aging. 2012;33:2282–90.PubMedCrossRefGoogle Scholar
  118. 118.
    Shah R. The role of nutrition and diet in Alzheimer disease: a systematic review. J Am Med Dir Assoc. 2013;14(6):398–402.PubMedCrossRefGoogle Scholar
  119. 119.
    Osakada F, Hashino A, Kume T, Katsuki H, Kaneko S, Akaike A. Alpha-tocotrienol provides the most potent neuroprotection among vitamin E analogs on cultured striatal neurons. Neuropharmacology. 2004;47:904–15.PubMedCrossRefGoogle Scholar
  120. 120.
    Yonguc G, Dodurga Y, Adiguzel E, Gundogdu G, Kucukatay V, Ozbal S, Yilmaz I, Cankurt U, Yilmaz Y, Akdogan I. Grape seed extract has superior beneficial effects than vitamin E on oxidative stress and apoptosis in the hippocampus of streptozotocin induced diabetic rats. Gene. 2015;555:119–26. doi: 10.1016/j.gene.2014.10.052.PubMedCrossRefGoogle Scholar
  121. 121.
    Mazlan M, Sue Mian T, Mat Top G, Zurinah Wan Ngah W. Comparative effects of alpha-tocopherol and gamma-tocotrienol against hydrogen peroxide induced apoptosis on primary-cultured astrocytes. J Neurol Sci. 2006;243:5–12.PubMedCrossRefGoogle Scholar
  122. 122.
    Lane M, Bailey S. Role of retinoid signalling in the adult brain. Prog Neurobiol. 2005;75:275–93.PubMedCrossRefGoogle Scholar
  123. 123.
    Campo-Paysaa F, Marlétaz F, Laudet V, Schubert M. Retinoic acid signaling in development: tissue-specific functions and evolutionary origins. Genesis. 2008;46:640–56.PubMedCrossRefGoogle Scholar
  124. 124.
    Luo T, Wagner E, Dräger U. Integrating retinoic acid signaling with brain function. Dev Psychol. 2009;45:139–50.PubMedCrossRefGoogle Scholar
  125. 125.
    Malaspina A, Michael-Titus AT. Is the modulation of retinoid and retinoid-associated signaling a future therapeutic strategy in neurological trauma and neurodegeneration? J Neurochem. 2008;104:584–95.PubMedGoogle Scholar
  126. 126.
    Cocco S, Diaz G, Stancampiano R, Diana A, Carta M, Curreli R, Sarais L, Fadda F. Vitamin A deficiency produces spatial learning and memory impairment in rats. Neuroscience. 2002;115:​475–82.PubMedCrossRefGoogle Scholar
  127. 127.
    Hernández-Pinto A, Puebla-Jiménez L, Arilla-Ferreiro E. A vitamin A-free diet results in impairment of the rat hippocampal somatostatinergic system. Neuroscience. 2006;141:851–61.PubMedCrossRefGoogle Scholar
  128. 128.
    Mingaud F, Mormede C, Etchamendy N, Mons N, Niedergang B, Wietrzych M, Pallet V, Jaffard R, Krezel W, Higueret P, Marighetto A. Retinoid hyposignaling contributes to aging-related decline in hippocampal function in short-term/working memory organization and long-term declarative memory encoding in mice. J Neurosci. 2008;28:279–91.PubMedCrossRefGoogle Scholar
  129. 129.
    Misner D, Jacobs S, Shimizu Y, deUrquiza AM, Solomin L, Perlmann T, De Luca LM, Stevens C, Evans R. Vitamin A deprivation results in reversible loss of hippocampal long-term synaptic plasticity. Proc Natl Acad Sci U S A. 2001;98:11714–9.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Kuenzli S, Tran C, Saurat J. Retinoid receptors in inflammatory responses: a potential target for pharmacology. Curr Drug Targets Inflamm Allergy. 2004;3:355–60.PubMedCrossRefGoogle Scholar
  131. 131.
    Kampmann E, Johann S, van Neerven S, Beyer C, Mey J. Anti-inflammatory effect of retinoic acid on prostaglandin synthesis in cultured cortical astrocytes. J Neurochem. 2008;106:320–32.PubMedCrossRefGoogle Scholar
  132. 132.
    Hashioka S, Han Y, Fujii S, Kato T, Monji A, Utsumi H, Sawada M, Nakanishi H, Kanba S. Phosphatidylserine and phosphatidylcholine-containing liposomes inhibit amyloid and interferon-induced microglial activation. Free Radic Biol Med. 2007;42:945–54.PubMedCrossRefGoogle Scholar
  133. 133.
    Kao T, Ou Y, Lin S, Pan H, Song P, Raung S, Lai C, Liao S, Lu H, Chen C. Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia. J Nutr Biochem. 2011;22:612–24.PubMedCrossRefGoogle Scholar
  134. 134.
    Benveniste EN. Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J Mol Med. 1997;75:165–73.PubMedCrossRefGoogle Scholar
  135. 135.
    Cameron B, Landreth GE. Inflammation, microglia, and Alzheimer’s disease. Neurobiol Dis. 2010;37:503–9.PubMedCrossRefGoogle Scholar
  136. 136.
    De Keyser J, Zeinstra E, Frohman E. Are astrocytes central players in the pathophysiology of multiple sclerosis? Arch Neurol. 2003;60:132–6.PubMedCrossRefGoogle Scholar
  137. 137.
    Dong Y, Benveniste E. Immune function of astrocytes. Glia. 2001;36:180–90.PubMedCrossRefGoogle Scholar
  138. 138.
    Van Neerven S, Nemes A, Imholz P, Regen T, Denecke B, Johann S, Beyer C, Hanisch UK, Mey J. Inflammatory cytokine release of astrocytes in vitro is reduced by all-trans retinoic acid. J Neuroimmunol. 2010;229:169–79.PubMedCrossRefGoogle Scholar
  139. 139.
    Chakrabarti M, McDonald A, Will Reed J, Moss M, Das B, Ray S. Mechanisms of natural and synthetic retinoids for inhibition of pathogenesis in Alzheimer’s disease. J Alzheimers Dis. 2015;50(2):335–52.PubMedCentralCrossRefGoogle Scholar
  140. 140.
    Wang R, Chen S, Liu Y, Diao S, Xue Y, You X, Park E, Liao F. All-trans-retinoic acid reduces BACE1 expression under inflammatory conditions via modulation of nuclear factor κB (NFκB) signaling. J Biol Chem. 2015;290(37):22532–42.PubMedPubMedCentralCrossRefGoogle Scholar
  141. 141.
    Patra R, Swarup D, Dwivedi S. Antioxidant effects of tocopherol, ascorbic acid and l-methionine on lead-induced oxidative stress to the liver, kidney and brain in rats. Toxicology. 2001;162:81–8.PubMedCrossRefGoogle Scholar
  142. 142.
    Ramanathan K, Balakumar B, Panneerselvam C. Effects of ascorbic acid and alpha-tocopherol on arsenic-induced oxidative stress. Hum Exp Toxicol. 2002;21:675–80.PubMedCrossRefGoogle Scholar
  143. 143.
    Peacock J, Folsom A, Knopman D, Mosley T, Goff Jr D, Szklo M. Dietary antioxidant intake and cognitive performance in middle-aged adults. The Atherosclerosis Risk in Communities (ARIC) Study investigators. Public Health Nutr. 2000;3(3):​337–43.PubMedCrossRefGoogle Scholar
  144. 144.
    Yonghua L, Shumei L, Yigand M, Ning L, Yu Z. Effects of vitamins E and C combined with β-carotene on cognitive function in the elderly. Exp Ther Med. 2015;9(4):1489–93.Google Scholar
  145. 145.
    Masaki KH, Losonczy KG, Izmirlian G, Foley DJ, Ross GW, Petrovitch H, Havlik R, White LR. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology. 2000;54(6):1265–72.PubMedCrossRefGoogle Scholar
  146. 146.
    Bowman G, Dodge H, Frei B, Calabrese C, Oken B, Kaye J, Quinn J. Ascorbic acid and rates of cognitive decline in Alzheimer’s disease. J Alzheimers Dis. 2009;16:93–8.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Mosdol A, Erens B, Brunner E. Estimated prevalence and predictors of vitamin C deficiency within UK’s low-income population. J Public Health Dent. 2008;30:456–60.CrossRefGoogle Scholar
  148. 148.
    Charlton K, Rabinowitz T, Geffen L, Dhansay M. Lowered plasma vitamin C, but not vitamin E, concentrations in dementia patients. J Nutr Health Aging. 2004;8:99–107.PubMedGoogle Scholar
  149. 149.
    Riviere S, Birlouez-Aragon I, Nourhashemi F, Vellas B. Low plasma vitamin C in alzheimer patients despite an adequate diet. Int J Geriatr Psychopharmacol. 1998;13:749–54.CrossRefGoogle Scholar
  150. 150.
    Murakami K, Murata N, Ozawa Y, Kinoshita N, Irie K, Shirasawa T, Shimizu T. Vitamin C restores behavioral deficits and amyloid- β oligomerization without affecting plaque formation in a mouse model of alzheimer’s disease. J Alzheimers Dis. 2011;​26:7–18.PubMedCrossRefGoogle Scholar
  151. 151.
    Kennard J, Harrison F. Intravenous ascorbate improves spatial memory in middle-aged APP/PSEN1 and wild type mice. Behav Brain Res. 2014;264:34–42.PubMedPubMedCentralCrossRefGoogle Scholar
  152. 152.
    Engelhart M, Geerlings M, Ruitenberg A, van Swieten J, Hofman A, Witteman J, Breteler M. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA. 2002;287:3223–9.PubMedCrossRefGoogle Scholar
  153. 153.
    Daly R, Gagnon C, Lu Z, Magliano D, Dunstan D, Sikaris K, Zimmet P, Ebeling P, Shaw J. Prevalence of vitamin D deficiency and its determinants in Australian adults aged 25 years and older: a national, population-based study. Clin Endocrinol. 2012;77:​26–35.CrossRefGoogle Scholar
  154. 154.
    Garcion E, Sindji L, Leblondel G, Brachet P, Darcy F. 1,25-Dihydroxyvitamin D3 regulates the synthesis of gamma-glutamyltranspeptidase and glutathione levels in rat primary astrocytes. J Neurochem. 1999;73:859–66.PubMedCrossRefGoogle Scholar
  155. 155.
    Eyles D, Smith S, Kinobe R, Hewison M, McGrath J. Distribution of the vitamin D receptor and 1[alpha]-hydroxylase in human brain. J Chem Neuroanat. 2005;29:21–30.PubMedCrossRefGoogle Scholar
  156. 156.
    Langub MC, Herman JP, Malluche HH, Koszewski NJ. Evidence of functional vitamin D receptors in rat hippocampus. Neuroscience. 2001;104:49–56.PubMedCrossRefGoogle Scholar
  157. 157.
    Balion C, Griffith L, Strifler L, Henderson M, Patterson C, Heckman G, Llewellyn D, Raina P. Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology. 2012;79:​1397–405.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Buell J, Dawson-Hughes B. Vitamin D and neurocognitive dysfunction: preventing “D” ecline? Mol Asp Med. 2008;29:415–22.CrossRefGoogle Scholar
  159. 159.
    Littlejohns T, Henley W, Lang I, Annweiler C, Beauchet O, Chaves P, Fried L, Kestenbaum B, Kuller L, Langa K, Lopez O, Kos K, Soni M, Llewellyn D. Vitamin D and the risk of dementia and Alzheimer disease. Neurology. 2014;83:920–8.PubMedPubMedCentralCrossRefGoogle Scholar
  160. 160.
    Taghizadeh M, Djazayery A, Salami M, Eshraghian MR, Zavareh SA. VitaminD-free regimen intensifies the spatial learning deficit in Alzheimer’ s disease. Int J Neurol. 2011;121:16–24.Google Scholar
  161. 161.
    Annweiler C, Rolland Y, Schott AM, Blain H, Vellas B, Beauchet O. Serum vitamin D deficiency as a predictor of incident non-Alzheimer dementias: a 7-year longitudinal study. Dement Geriatr Cogn Disord. 2011;32:273–8.PubMedCrossRefGoogle Scholar
  162. 162.
    Annweiler C, Maby E, Meyerber M, Beauchet O. Hypovitaminosis D and executive dysfunction in older adults with memory complaint: a memory clinic-based study. Dement Geriatr Cogn Disord. 2014;37:286–93.PubMedCrossRefGoogle Scholar
  163. 163.
    Ito S, Ohtsuki S, Nezu Y, Koitabashi Y, Murata S, Terasaki T. 1alpha,25-Dihydroxyvitamin D3 enhances cerebral clearance of human amyloid-beta peptide(1–40) from mouse brain across the blood–brain barrier. Fluids Barriers CNS. 2011;8:20.PubMedPubMedCentralCrossRefGoogle Scholar
  164. 164.
    Masoumi A, Goldenson B, Set G. 1α25-dihydroxyvitamin D3 interacts with curcuminoids to stimulate amyloid-β clearance by macrophages of Alzheimer’s disease patients. J Alzheimer’s Dis. 2009;17:703–17.Google Scholar
  165. 165.
    Kim D, Nguyen M, Dobbin M, Fischer A, Sananbenesi F, Rodgers J, Delalle I, Baur J, Sui G, Armour S, Puigserver P, Sinclair D, Tsai L. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J. 2007;26(13):3169–79.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Venturini C, Merlo S, Souto A, Fernandes M, Gomez R, Rhoden C. Resveratrol and red wine function as antioxidants in the nervous system without cellular proliferative effects during experimental diabetes. Oxidative Med Cell Longev. 2010;3:434–41.CrossRefGoogle Scholar
  167. 167.
    Ye J, Liu Z, Wei J, Lu L, Huang Y, Luo L. Protective effect of SIRT1 on toxicity of microglial-derived factors induced by LPS to PC12 cells via the p53-caspase-3-dependent apoptotic pathway. Neurosci Lett. 2013;553:72–7.PubMedCrossRefGoogle Scholar
  168. 168.
    Carrizzo A, Forte M, Damato A, Trimarco V, Salzano F, Bartolo M, Maciag A, Puca A, Vecchione C. Antioxidant effects of resveratrol in cardiovascular, cerebral and metabolic diseases. Food Chem Toxicol. 2013;61:215–26.PubMedCrossRefGoogle Scholar
  169. 169.
    Wang H, Yang Y, Qian J, Zhang Q, Xu H, Li J. Resveratrol in cardiovascular disease: what is known from current research? Heart Fail. Review. 2012;17:437–48.Google Scholar
  170. 170.
    Liu B, Hong J. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther. 2003;304:1–7.PubMedCrossRefGoogle Scholar
  171. 171.
    Capiralla H, Vingtdeux V, Zhao H, Sankowski R, Al-Abed Y, Davies P, Marambaud P. Resveratrol mitigates lipopolysaccharide- and Aβ-mediated microglial inflammation by inhibiting the TLR4/NF-κB/STAT signaling cascade. J Neurochem. 2012;120(3):461–72.PubMedCrossRefGoogle Scholar
  172. 172.
    Karuppagounder S, Pinto J, Xu H, Chen H, Beal M, Gibson G. Dietary supplementation with resveratrol reduces plaque pathology in a transgenic mouse model of Alzheimer’s disease. Neurochem Int. 2009;28:1393–405.Google Scholar
  173. 173.
    Marambaud P, Zhao H, Davies P. Resveratrol promotes clearance of Alzheimer’s disease amyloid-b peptides. J Biol Chem. 2005;280:37377–82.PubMedCrossRefGoogle Scholar
  174. 174.
    Ono K, Naiki H, Yamada M. The development of preventives and therapeutics for Alzheimer’s disease that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta. Curr Pharm Des. 2006;12:4357–75.PubMedCrossRefGoogle Scholar
  175. 175.
    Vingtdeux V, Giliberto L, Zhao H, Chandakkar P, Wu Q, Simon J. AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. J Biol Chem. 2010;285:​9100–13.PubMedPubMedCentralCrossRefGoogle Scholar
  176. 176.
    Porquet D, Casadesús G, Bayod S, Vicente A, Canudas A, Vilaplana J. Dietary resveratrol prevents Alzheimer’s markers and increases life span in SAMP8. Age (Dordr). 2013;35:1851–65.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Silvina Monica Alvarez
    • 1
  • Nidia N. Gomez
    • 1
  • Lorena Navigatore Fonzo
    • 1
  • Emilse S. Sanchez
    • 1
  • María Sofía Giménez
    • 1
  1. 1.Universidad Nacional de San Luis, IMIBIO SL, CONICET, Bioquimica y Ciencias BiologicasSan LuisArgentina

Personalised recommendations