Chapter 16 : Antioxidants and Brain Function in HIV/AIDS

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Antioxidants and Brain Function in HIV/AIDS, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815691/9781555813697_Chap16-1.gif /docserver/preview/fulltext/10.1128/9781555815691/9781555813697_Chap16-2.gif


Impaired neuroprotection, due to increased oxidative stress, has been implicated as a factor affecting neuronal degeneration in HIV/AIDS. This chapter reviews the role of biological antioxidants in maintaining adequate brain function in HIV-1 disease. Cognitive impairment is the major neurological complication of HIV-1 infection, ranging in severity from a mild subclinical cognitive deficit to a dementing illness (HIV-1- associated dementia [HAD]). The advent of protease inhibitors has raised the possibility of HIV-1 suppression and potential eradication, as well as potential neuropsychological benefit. Treatment with highly active antiretroviral therapy (HAART) appears to produce a beneficial effect on neurocognitive functioning. Microglial activation, through the mediation of oxidative stress, appears to play a major role in neuronal apoptosis and consequent neuronal loss in HIV-1-infected individuals. Antioxidants may also decrease neuropathogenesis through regulation of specific proinflammatory cytokines that contribute to neurodegenerative changes and are evident in HIV-1 disease. Alterations in nutritional status have long been acknowledged in various HIV-1-infected cohorts, including men who have sex with men, drug users, heterosexual adults, and children. Antioxidative treatment (daily intake of selenium, vitamin E, and vitamin C) has been reported to inhibit progression of mental deterioration in patients with multiple sclerosis. Moreover, antioxidant therapies have been reported to slow the progression of Alzheimer’s disease and improve cognitive function in late life for those without dementia.

Citation: Shor-Posner G, Campa A, Miguez-Burbano M, Castillo G, Moreno-Black G. 2009. Antioxidants and Brain Function in HIV/AIDS, p 219-230. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch16
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Cytokines in HIV neuropathogenesis. Imbalanced cytokines (proinflammatory versus anti-inflammatory) in the brain tissue of HIV-infected individuals.

Citation: Shor-Posner G, Campa A, Miguez-Burbano M, Castillo G, Moreno-Black G. 2009. Antioxidants and Brain Function in HIV/AIDS, p 219-230. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Potential action of selenium in reducing oxidative stress through its role in glutathione peroxidase activity, which protects the brain against lipoperoxidation. Cells are susceptible to the damaging actions of the small amounts of , OH, and HO that inevitably form during metabolism, especially in the reduction of oxygen by the electron transfer system of mitochondria. Free reactive oxygen species react with lipids, particularly polyunsaturated fatty acids, initiating a process known as lipid peroxidation, and subsequent production of new reactive species. Both O and HO need to be quickly removed from the system and, in general, are reduced by enzyme detoxification, involving catalase and selenium-dependent glutathione peroxidase (Se-GPx), the major protective enzyme against excessive oxidative stress in the brain.

Citation: Shor-Posner G, Campa A, Miguez-Burbano M, Castillo G, Moreno-Black G. 2009. Antioxidants and Brain Function in HIV/AIDS, p 219-230. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

Selenium and cytokine regulation. The rationale for a selenium-cytokine mechanism of action in neuroprotection has been demonstrated in studies indicating the potential for selenium to decrease neuropathogenesis through suppression of IL-induced HIV-1 replication and neuronal apoptosis ( ).

Citation: Shor-Posner G, Campa A, Miguez-Burbano M, Castillo G, Moreno-Black G. 2009. Antioxidants and Brain Function in HIV/AIDS, p 219-230. In Goodkin K, Shapshak P, Verma A (ed), The Spectrum of Neuro-AIDS Disorders. ASM Press, Washington, DC. doi: 10.1128/9781555815691.ch16
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Abrams, B.,, D. Duncan, and, I. Hertz-Picciotto. 1993. A prospective study of dietary intake and acquired immune deficiency syndrome in HIV-seropositive homosexual men. J. Acquir. Immune Defic. Syndr. 6: 949.
2. Adamson, D.,, B. Wildemann,, M. Sasaki,, J. Glass,, J. McArthur,, V. Christov,, T. Dawson, and, V. Dawson. 1996. Immunologic NO synthase: elevation in severe AIDS dementia and induction by HIV-1gp41. Science 274: 19171921.
3. Alciati, A.,, F. Starace,, B. Scaramelli,, M. Campaniello,, B. Adriani,, C. Mellado, and, A. Cargnel. 2001. Has there been a decrease in the prevalence of mood disorders in HIV-seropositive individuals since the introduction of combination therapy? Eur. Psychiatry 16: 491496.
4. Allard, J.,, E. Aghdassi,, J. Chau,, C. Tam C. Kovacs,, I. Salit, and, S. Walmsley. 1998. Effects of vitamin E and C supplementation on oxidative stress and viral load in HIV-infected subjects. AIDS 12: 16531659.
5. American Academy of Neurology Task Force. 1991. Nomenclature and research case definitions for neurologic manifestations of human immunodeficiency virus-type 1 (HIV-1) infection. Neurology 41: 778785.
6. Aukrust, P.,, F. Muller,, A. Svardal,, T. Ueland,, R. Berge, and, S. Froland. 2003. Disturbed glutathione metabolism and decreased antioxidant levels in human immunodeficiency virus-infected patients during highly active antiretroviral therapy-potential immunomodulatory effects of antioxidants. J. Infect. Dis. 188: 232238.
7. Baldewicz, T.,, K. Goodkin,, N. Blaney,, G. Shor-Posner,, M. Kumar,, F. Wilkie,, M. Baum, and, C. Eisdorfer. 2000. Cobalamin level is related to self-reported and clinically related mood and to syndromal depression in bereaved HIV-1+ and HIV-1 homosexual men. J. Psychosom. Res. 48: 177185.
8. Baldewicz, T.,, K. Goodkin,, D. Feaster,, N. Blaney,, M. Kumar,, A. Kumar,, G. Shor-Posner, and, M. Baum. 1998. Plasma pyridoxine deficiency is related to increased psychological distress in recently bereaved homosexual men. Psychosom. Med. 60: 297308.
9. Baum, M.,, G. Shor-Posner,, S. Lai,, G. Zhang,, H. Lai,, M. Fletcher,, H. Sauberlich, and, J. Page. 1997. High risk of HIV-related mortality is associated with selenium deficiency. J. Acquir. Immune Defic. Syndr. 15: 370374.
10. Beach, R.,, E. Mantero-Atienza,, G. Shor-Posner,, J. Javier,, J. Szapocznik,, R. Morgan,, H. Sauberlich,, P. Cornwell,, C. Eisdorfer, and, M. Baum. 1992. Specific nutrient abnormalities in asymptomatic HIV-1 infection. AIDS 6: 701708.
11. Bell, J.,, Y. Donaldson,, S. Lowrie,, C. McKenzie,, R. Elton,, A. Chiswick,, R. Brettle,, J. Ironside, and, P. Simmonds. 1996. Influence of risk group and zidovudine therapy on the development of HIV encephalitis and cognitive impairment in AIDS patients. AIDS 10: 493499.
12. Benton, D.,, and R. Cook. 1991. The impact of selenium supplementation on mood. Biol. Psychiatry 29: 10921098.
13. Berger, J.,, A. Nath,, R. Greenberg,, A. Andersen,, R. Greene,, R. Bognar, and, M. Avison. 2000. Cerebrovascular changes in the basal ganglia with HIV dementia. Neurology 54: 921926.
14. Bilici, M.,, H. Efe,, M. Koroglu,, H. Uyda,, M. Bekaroglu, and, O. Deger. 2001. Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J. Affect. Disord. 64: 4351.
15. Bjugstad, K.,, W. Flitter,, W. Garland,, G. Su, and, G. Arendash. 1998. Preventive actions of a synthetic antioxidant in a novel animal model of AIDS dementia. Brain Res. 795: 349357.
16. Boos, J. 2000. Chronic-treated HIV: a neurologic disease. J. Urban Health 7: 204212.
17. Boven, L.,, L. Gomez,, C. Hery,, F. Gray,, J. Verhoef,, P. Portegies,, M. Tardieu, and, H. Nottet. 1999. Increased peroxynitrite activity in AIDS dementia complex: implications for the neuropathogenesis of HIV-1 infection. Immunology 162: 43194327.
18. Boven, L.,, J. Middel,, C. Hery,, F. Gray,, P. Verhoef P. Portegies,, M. Tardieu, and, H. Nottet. 1998. Increased peroxynitrite activity and elevated neurotrophin levels in brains of patients with AIDS dementia complex. Neuroscience of HIV infection. J. Neurovirol. 4: 343.
19. Brechtl, J.,, W. Breitbart,, M. Galietta,, S. Krivo, and, B. Rosenfeld. 2001. The use of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection: impact on medical, palliative care, and quality of life outcomes. J. Pain Symptom Manage. 21: 4151.
20. Brigelius-Flohe, R.,, B. Friedrichs,, S. Maurer,, M. Schultz, and, R. Streicher. 1997. Interleukin 1-induced nuclear factor kappa B activation is inhibited by overexpression of phospholipid hydroperoxide glutathione peroxidase in a human endothelial cell line. Biochem. J. 328: 199203.
21. Burnet, F. 1981. A possible role of zinc in the pathology of dementia. Lancet 1: 186188.
22. Campa, A.,, G. Shor-Posner,, F. Indacochea,, G. Zhang,, H. Lai,, D. Asthana,, G. Scott, and, M. Baum. 1999. Mortality risk in selenium-deficient HIV-positive children. J. Acquir. Immun. Defic. Syndr. 20: 508513.
23. Carethers, M. 1988. Diagnosing vitamin B12 deficiency: a common geriatric disorder. Geriatrics 43: 89112.
24. Chauhan, A.,, J. Turchan,, C. Pocernich,, A. Bruce-Keller,, S. Roth,, D. Butterfield,, E. Major, and, A. Nath. 2003. Intracellular human immunodeficiency virus Tat expression in astrocytes promotes astrocyte survival but induces potent neurotoxicity at distant sites via axonal transport. J. Biol. Chem. 278: 1351213519.
25. Chiesi, A.,, S. Vella,, L. Dally,, C. Pedersen,, S. Danner,, A. Johnson,, S. Schwander,, F. Goebel,, H. Glauser, and, F. Antunes. 1996. Epidemiology of AIDS dementia complex in Europe. J. Acquir. Immune Defic. Syndr. 11: 3944.
26. Cirelli, A.,, M. Ciard,, C. DeSimone,, F. Sonce,, R. Giordano,, L. Ciaralli, and, S. Constantini. 1991. Serum selenium concentration and disease progress in patients with HIV infection. Clin. Biochem. 24: 211214.
27. Clausen, J.,, G. Jensen, and, S. Nielsen. 1988. Selenium in chronic neurologic diseases. Multiple sclerosis and Batten’s disease. Biol. Trace Elem. Res. 15: 179203.
28. Cohen, R.,, R. Boland,, R. Paul,, K. Tashima,, E. Schoenbaum,, D. Celentano,, P. Schuman,, D. Smith, and, C. Carpenter. 2001. Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women. AIDS 15: 341345.
29. Conant, K.,, A. Garzino-Demo, A. Nath,, J. McArthur,, W. Halliday,, C. Power,, R. Gallo, and, E. Major. 1998. Induction of monocyte chemoattractant protein-1 in HIV-1 Tat stimulated astrocytes and elevation in AIDS dementia. Proc. Natl. Acad. Sci. USA 95: 31173121.
30. Coyle, J.,, and P. Puttfarcken. 1993. Oxidative stress, glutamate, and neurodegenerative disorders. Science 262: 689.
31. Dana Consortium on the Therapy of HIV Dementia and Related Cognitive Disorders. 1998. A randomized, double-blind, placebo-controlled trial of deprenyl and thioctic acid in human immunodeficiency virus-associated cognitive impairment. Neurology 50: 645651.
32. Delmas-Beauvieux, M.,, E. Peuchant,, A. Couchoron,, J. Constans,, C. Sergeant,, M. Simonoff,, J. Pellegrin,, B. Leng,, C. Conri, and, M. Clerc. 1996. The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients: effects of supplementation with selenium or B-carotene. Am. J. Clin. Nutr. 64: 101107.
33. Diplock, A. 1994. Antioxidants and disease prevention. Mol. Aspects Med. 15: 293376.
34. di Ronchi, D.,, I. Faranca,, P. Forti,, G. Ravaghia,, M. Borderi,, R. Manfredi, and, V. Volterra. 2000. Development of acute psychotic disorders and the HIV-1 infection. Int. J. Psychiatry Med. 30: 173183.
35. Dobmeyer, T.,, S. Findhammer,, J. Dobmeyer,, S. Klein,, B. Raffel,, D. Hoelzer,, E. Helm,, D. Kabelitz, and, R. Rossol. 1997. Ex vivo induction of apoptosis in lymphocytes is mediated by oxidative stress: role for lymphocyte loss in HIV infection. Free Radic. Biol. Med. 22: 775785.
36. Dore, G.,, P. Correll,, Y. Li,, J. Kaldor,, D. Cooper, and, B. Brew. 1999. Changes to AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 9: 12491253.
37. Dreyfuss, P. 1988. Diet and nutrition in neurologic disorder, p. 1458–1470. In M. Shils and, Y. Young (ed.), Modern Nutrition in Health and Disease. Lea & Febiger, Philadelphia, PA.
38. Engelhart, M.,, M. Geerlings,, A. Ruitenberg,, J. van Swieten,, A. Hofman,, J. Witteman, and, M. Breteler. 2002. Dietary intake of antioxidants and risk of Alzheimer disease. JAMA 287: 32233229.
39. Epstein, L.,, and H. Gerbard. 1999. HIV-1-induced neuronal injury in the developing brain. J. Leukoc. Biol. 65: 453457.
40. Eugenin, E. A.,, J. E. King,, A. Nath,, T. M. Calderon,, R. S. Zukin,, M. V. Bennett, and, J. W. Berman. 2007. HIV-tat induces formation of an LRP-PSD-95-NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc. Natl. Acad. Sci. USA 104: 34383443.
41. Evans, D.,, G. Edelsohn, and, R. Golden. 1983. Organic psychosis without anemia or spinal cord symptoms in patients with vitamin B12 deficiency. Am. J. Psychiatry 140: 218221.
42. Favier, A.,, C. Sappey,, P. Leclerc,, P. Faure, and, M. Micoud. 1994. Antioxidant status and lipid peroxidation in patients infected with HIV. Chem. Biol. Interact. 91: 165.
43. Fine, S.,, R. Angel,, S. Perry,, L. Epstein,, J. Rothstein,, S. Dewhurst, and, H. Gerbard. 1996. Tumor necrosis factor α inhibits glutamate uptake by primary human astrocytes: implications for pathogenesis of HIV-1 dementia. J. Biol. Chem. 27: 15303.
44. Geagea, K.,, and J. Ananth. 1975. Response of a psychiatric patient to vitamin B12 therapy. Dis. Nerv. Syst. 36: 343344.
45. Giovannoni, G.,, R. Miller,, S. Heales,, J. Land,, M. Harrison, and, E. Thompson. 1998. Elevated cerebrospinal fluid and serum nitrate and nitrite levels in patients with central nervous system complications of HIV-1 infection: a correlation with blood-brain-barrier dysfunction. J. Neurol. Sci. 156: 5358.
46. Gray, F. 1997. Lesions of the central nervous system in the early stages of human immunodeficiency virus. Rev. Neurol. 153: 629640.
47. Gray, F.,, H. Adle-Biassette,, F. Brion,, T. Ereau,, I. le Maner,, V. Levy, and, G. Crocket. 2000. Neuronal apoptosis in human immunodeficiency virus infection. J. Neurovirol. 6 (Suppl. 1) : S38S43.
48. Greenspan, H.,, and O. Aruoma. 1994. Oxidative stress and apoptosis in HIV infection: a role for plant-derived metabolites with synergistic antioxidant activity. Immunol. Today 15: 209.
49. Grunfeld, C.,, and D. Kotler. 1992. Wasting in the acquired immunodeficiency syndrome. Semin. Liver Dis. 12: 175187.
50. Halliwell, B.,, and J. Gutteridge. 1985. Oxygen radicals in the nervous system. Trends Neurosci. 8: 2226.
51. Harman, D. 1982. The free radical theory of aging, p. 255–275. In W. Pryor (ed.), Free Radicals in Biology. Academic Press, New York, NY.
52. Haslett, P. 1998. Anticytokine approaches to the treatment of anorexia and cachexia. Semin. Oncol. 25: 5357.
53. Hassine, D.,, F. Gray,, R. Chekroun,, F. Chretien,, B. Marc,, M. Durigon, and, E. Schouman-Claeys. 1995. Early cerebral lesions in HIV infection. Postmortem radio-pathologic correlations in non-AIDS asymptomatic seropositive patients. J. Neuroradiol. 22: 148160.
54. Hawkes, W.,, and L. Hornbostel. 1996. Effects of dietary selenium on mood in healthy men living in a metabolic research unit. Biol. Psychiatry 39: 121128.
55. Healton, E.,, D. Savage,, J. Brust,, T. Garrett, and, J. Lindenbaum. 1991. Neurologic aspects of cobalamin deficiency. Medicine 70: 229245.
56. Heaton, R.,, R. Velin,, J. McCutchan,, S. Gulevich,, H. Atkinson,, M. Wallace,, H. Godfrey,, D. Kirson,, I. Grant, and the HNRC. 1994. Neuropsychological impairment in human immunodeficiency virus-infection: implications for employment. Psychosom. Med. 56: 817.
57. Henkin, R.,, B. Patten,, P. Re, and, D. Bronzert. 1975. A syndrome of acute zinc loss. Cerebellar dysfunction, mental changes, anorexia, and taste and smell dysfunction. Arch. Neurol. 32: 745751.
58. Herzlich, B.,, and T. Schiano. 1993. Reversal of apparent AIDS dementia complex following treatment with vitamin B12. J. Intern. Med. 233: 495497.
59. Hirano, F.,, H. Tanaka,, T. Miura,, Y. Hirano,, K. Okamoto,, Y. Makino, and, I. Makino. 1998. Inhibition of NH-kB-dependent transcription of human immunodeficiency virus 1 promoter by a phosphodiester compound of vitamin C and vitamin E, EPC-K1. Immunopharmacology 39: 3138.
60. Hori, K.,, D. Hatfield,, F. Maldarelli,, B. Lee, and, K. Close. 1997. Selenium supplementation suppresses tumor necrosis factor alpha-induced human immunodeficiency virus replication in vitro. AIDS 13: 13251332.
61. Ikeda, K.,, T. Nagashima,, S. Wu,, M. Yamaguchi, and, N. Tamaki. 1997. The role of calcium ion in anoxide/regoxygenation damage of cultured brain capillary endothelial cells. Acta Neurochir. Suppl. 70: 47.
62. Israel, N.,, and M. Gougerot-Pocidalo. 1997. Oxidative stress in human immunodeficiency virus infection. Cell. Mol. Life Sci. 53: 864870.
63. Jariwalla, R. 1995. Micronutrient imbalance in HIV infection and AIDS: relevance to pathogenesis and therapy. J. Nutr. Environ. Med. 5: 297.
64. Jarstrand, C.,, B. Akerlund, and, B. Lindeke. 1990. Glutathione and HIV infection. Lancet i: 235.
65. Judd, F.,, A. Cockram,, A. Komiti,, A. Mijch,, J. Hoy, and, R. Bell. 2000. Depressive symptoms reduced in individuals with HIV/AIDS treated with highly active antiretroviral therapy: a longitudinal study. Aust. N. Z. J. Psychiatry 34: 10151021.
66. Ketzler, S.,, S. Weiss,, H. Hung, and, H. Budka. 1990. Loss of neurons in the frontal cortex in AIDS brains. Acta Kieb. Neuropathol. 80: 9294.
67. Kieburtz, K.,, D. Giang,, R. Schiffer, and, N. Vakil. 1991. Abnormal vitamin B 12 metabolism in human immunodeficiency virus infection. Association with neurological dysfunction. Arch. Neurol. 48: 312314.
68. Kilbourne, A.,, A. Justice,, L. Rabeneck,, M. Rodriguez-Barrdas,, S. Weissman, and The VACS 3 Project Team. 2001. General medical and psychiatric comorbidity among HIV-infected veterans in the post-HAART era. J. Clin. Epidemiol. 54: S22S28.
69. Kruman, I.,, A. Nath, and, M. Mattson. 1998. HIV-1 protein Tat induces apoptosis of hippocampal neurons by a mechanism involving caspase activation, calcium overload, and oxidative stress. Exp. Neurol. 154: 276288.
70. Kupka, R.,, and W. Fawzi. 2002. Zinc nutrition and HIV infection. Nutr. Rev. 60: 6979.
71. Kusdra, L.,, D. McGuire, and, L. Pulliam. 2002. Changes in monocyte/macrophage neurotoxicity in the era of HAART. Implications for HIV-associated dementia. AIDS 16: 3138.
72. Lai, H.,, S. Lai,, G. Shor-Posner,, M. Fangcho,, E. Trapido, and, M. Baum. 2001. Plasma zinc, copper, copper:zinc ratio and survival in a cohort of HIV-1 infected homosexual men. J. Acquir. Immune Defic. Syndr. 27: 5662.
73. Larrick, J. 1994. Metabolism of arginine to nitric oxide: an area for nutritional manipulation of human disease? J. Optimal Nutr. 3: 2231.
74. Lee, Y.,, J. Satoh,, D. Walker, and, S. Kim. 1996. Interleukin-15 gene expression in human astrocytes and microglia in culture. Neuroreport 7: 10621066.
75. Lin, Y.,, A. Desbois,, S. Jiang, and, S. Hou. 2004. Group B vitamins protect murine cerebellar granule cells from glutamate/NMDA toxicity. Neuroreport 15: 22412244.
76. Lonn, E.,, J. Busch,, S. Yusuf,, P. Sheridan,, J. Pogue,, J. M. O. Arnold,, C. Ross,, A. Arnold,, P. Sleight,, J. Probstfield, and, G. R. Dagenais. 2005. Effects of long term vitamin E supplementation on cardiovascular events and cancer in a randomized controlled trial. New Engl. J. Med. 293: 13381347.
77. Look, M.,, J. Rockstroh,, G. Rao,, K. Kreuzer,, S. Barton,, H. Lemoch,, T. Sudhop,, J. Hoch,, K. Stockings,, U. Spengler, and, T. Sauerbruch. 1997. Serum selenium, plasma glutathione (GSH) and erythrocyte glutathione peroxidase (GSH-PS) levels in asymptomatic versus symptomatic human immunodeficiency virus-1 (HIV-1) infection. Eur. J. Clin. Nutr. 51: 266272.
78. Lovell, M.,, W. Ehmann,, S. Butler, and, W. Markesbery. 1995. Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer’s disease. Neurology 45: 15941601.
79. Luchsinger, J.,, M. Tang,, S. Shea, and, R. Mayeux. 2003. Antioxidant vitamin intake and risk of Alzheimer disease. Arch. Neurol. 60: 203208.
80. Maragos, W.,, K. Young,, J. Turchan,, M. Guseva,, J. Pauly,, A. Nath, and, W. Cass. 2002. Human immunodeficiency virus-1 Tat protein and methamphetamine interact synergistically to impair striatal dopaminergic function. J. Neurochem. 83: 955963.
81. Masaki, K.,, K. Losonczy,, G. Izmirlian,, D. Foley,, G. Ross,, H. Petrovitch,, R. Halik, and, L. White. 2000. Association of vitamin E and C supplement use with cognitive function and dementia in elderly men. Neurology 54: 12651272.
82. Masaki, K.,, L. White,, H. Petrovic, et al. 1995. Superior cognitive functioning in later life. Neurology 45: A271A272.
83. Matsumoto, T.,, T. Miike,, R. Nelson,, W. Trudeau,, R. Lockey, and, J. Yoddoi. 1993. Elevated serum levels of IL-8 in patients with HIV infection. Clin. Exp. Immunol. 93: 149.
84. Matsuyama, T.,, N. Kobayashi, and, N. Yamamoto. 1991. Cytokines and HIV infection--is AIDS a tumor necrosis factor disease. AIDS 5: 1405.
85. Mayeux, R.,, Y. Stern,, M. Tang,, G. Todak,, K. Masarder,, M. Sano,, M. Richard,, Z. Stein,, A. Ehrhardt, and, J. Gorman. 1991. Mortality risks in gay men with human immunodeficiency virus infection and cognitive impairment. Neurology 43: 176182.
86. McFadden, S. 1996. Phenotypic variation in xenobiotic metabolism and adverse environmental response: focus on sulfur-dependent detoxification pathways. Toxicology 111: 4365.
87. Minagar, A.,, P. Shapshak,, R. Fujimura,, R. Ownby,, M. Heyes, and, C. Eisdorfer. 2002. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J. Neurol. Sci. 202: 13.
88. Mollace, V.,, H. Nottet,, P. Clayette,, M. Turco,, C. Muscoli,, D. Salvemini, and, C. Perno. 2001. Oxidative stress and neuroAIDS: triggers, modulators and novel antioxidants. Trends Neurosci. 24: 411416.
89. Morris, M.,, L. Beckett,, P. Scherr,, L. Hebert,, D. Bennett,, T. Field, and, D. Evans. 1998. Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis. Assoc. Disord. 12: 121126.
90. Moutet, M.,, P. d’Alessio,, P. Malette,, V. Devaux, and, J. Chaudiere. 1998. Glutathione peroxidase mimics prevent TNF and neutrophil induced endothelial alterations. Free Radic. Biol. Med. 25: 270281.
91. Moynagh, P.,, D. Williams, and, L. O’Neill. 1994. Activation of NF-kappa B and induction of vascular cell adhesion molecule-1 and intracellular adhesion molecule-1 expression in human glial cells by IL-1. Modulation by antioxidants. J. Immunol. 153: 26812690.
92. Neve, J. 1996. Selenium as a risk factor for cardiovascular diseases. J. Cardiovasc. Risk 3: 4247.
93. Newbold, H. 1989. Vitamin B-12: placebo or neglected therapeutic tool? Med. Hypotheses 28: 155164.
94. Noseworthy, M.,, and T. Bray. 1998. Effect of oxidative stress on brain damage detected by MRI and in vivo 31P-NMR. Free Radic. Biol. Med. 24: 942951.
95. Noseworthy, M.,, and T. Bray. 2000. Zinc deficiency exacerbates loss in blood-brain barrier integrity induced by hyperoxide measured by dynamic MRI. Proc. Soc. Exp. Biol. Med. 223: 175182.
96. O’Donnell, E.,, and M. Lynch. 1998. Dietary antioxidant supplementation reverses age-related neuronal changes. Neurobiol. Aging 19: 461467.
97. Owen, A.,, M. Batterham,, Y. Probst,, B. Grenyer, and, L. Tapsell. 2005. Low plasma vitamin E in major depression: diet or disease? Eur. J. Clin. Nutr. 59: 304306.
98. Oztas, B.,, S. Kilac,, E. Dural, and, T. Ispir. 2001. Influence of antioxidants on the blood-brain barrier permeability during epileptic seizures. J. Neurosci. Res. 66: 674678.
99. Pace, G.,, and C. Leaf. 1995. The raise of oxidative stress in HIV disease. Free Radic. Biol. Med. 19: 523528.
100. Parkinson Study Group. 1993. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N. Engl. J. Med. 328: 176183.
101. Penland, J.,, and J. Finley. 1995. Dietary selenium and mood states in healthy young men. N. Dakota Acad. Sci. Proc. 49: 26.
102. Penland, J.,, H. Sandstead,, N. Alcock,, H. Dayal,, X. Chen,, J. Li,, F. Zhao, and, J. Yang. 1997. A preliminary report: effects of zinc and micronutrient repletion on growth and neuropsychological function of urban Chinese children. J. Am. Coll. Nutr. 16: 268272.
103. Penland, J.,, H. Sandstead,, N. Egger,, H. Dayal,, N. Alcock,, R. Plotkin,, C. Rocco, and, A. Zavaleta. 1999. Zinc, iron and micronutrient supplementation effectis on cognitive and psychomotor function of Mexican-American school children. FASEB J. 13: A921.
104. Perlmutter, D. 1999. Functional therapeutics in neurodegenerative disease. J. Applied Nutr. 51: 313.
105. Persidsky, Y. 1999. Model systems for studies of leukocyte migration across the blood-brain barrier. J. Neurovirol. 5: 579590.
106. Phillips, S.,, and K. Kahaner. 1988. An unusual presentation of vitamin B12 deficiency. Am. J. Psychiatry 145: 529.
107. Pocernich, C.,, R. Sultana,, H. Mohmmad-Abdul,, A. Nath, and, D. Butterfield. 2005. HIV-dementia, Tat-induced oxidative stress, and antioxidant therapeutic considerations. Brain Res. Brain Res. Rev. 50: 1426.
108. Polidori, M.,, P. Mecocci, and, B. Frei. 2001. Plasma vitamin C levels are decreased and correlated with brain damage in patients with intracranial hemorrhage or head trauma. Stroke 32: 898902.
109. Porta, E. 1998. Role of oxidative damage in the aging process, p. 1–52. In C. Chow (ed.), Cellular Antioxidant Defense Mechanisms. CRC Press, Boca Raton, FL.
110. Prasad, A. D. 2007. Zinc: mechanisms of host defense. J. Nutrition 137: 13451349.
111. Prasad, A.,, P. Rabbani, and, A. Abbash. 1978. Experimental zinc deficiency in humans. Ann. Intern. Med. 89: 483.
112. Price, R. W.,, L. G. Epstein,, J. T. Becker,, P. Cinque,, M. Gisslen,, L. Pulliam, and, J. C. McArthur. 2007. Biomarkers of HIV-1 CNS infection and injury. Neurology 69: 17811788.
113. Pu, H.,, J. Tian,, I. Andras,, K. Hayashi,, G. Flora,, B. Hennig, and, M. Toborek. 2005. HIV Tat protein-induced alterations of ZO-1 expression are mediated by redox-regulated ERK1/2 activation. J. Cereb. Blood Flow Metab. 25: 13251335.
114. Pulliam, L.,, R. Gascon,, M. Stubblebine,, D. McGuire, and, M. McGrath. 1997. Unique monocyte subset in patients with AIDS dementia. Lancet 349: 692695.
115. Rabkin, J.,, S. Ferrando,, S. Lin,, M. Sewell, and, M. McElhiney. 2000. Psychological effects of HAART: a 2-year study. Psychosom. Med. 62: 413422.
116. Raemaekers, V.,, M. Calomme,, D. Vanden Berghe, et al. 1994. Selenium deficiency triggering intractable seizures. Neuropediatrics 25: 217223.
117. Rausch, D.,, and M. Davis. 2001. HIV in the CNS: pathogenic relationships to systemic HIV disease and other CNS diseases. J. Neurovirol. 7: 8596.
118. Remacha, A.,, J. Cadafalch,, P. Sarda,, M. Barcelo, and, M. Fuster. 2003. Vitamin B-12 metabolism in HIV-infected patients in the age of highly active antiretroviral therapy: role of homocysteine in assessing vitamin B-12 status. Am. J. Clin. Nutr. 77: 420424.
119. Roederer, M.,, F. Stall,, P. Raju,, S. Ela, and, L. Herzenberg. 1990. Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-l-cysteine. Proc. Natl. Acad. Sci. USA 87: 4884.
120. Ronaghy, H.,, J. Reinhold,, M. Mahloudji,, P. Ghavami,, M. Fox, and, J. Halsted. 1974. Zinc supplementation of malnourished schoolboys in Iran: increased growth and other effects. Am. J. Clin. Nutr. 27: 112121.
121. Rousseau, M.,, C. Molines,, J. Moreau, and, J. Delmont. 2000. Influence of highly active antiretroviral therapy on micronutrient profiles in HIV-infected patients. Ann. Nutr. Metab. 44: 212216.
122. Roy, M.,, L. Kiremidjian-Schumacher,, H. Wishe,, M. Cohen, and, G. Stotzky. 1993. Selenium supplementation enhances the expression of interleukin 2 receptor subunits and internalization of interleukin 2. Proc. Soc. Exp. Biol. Med. 202: 231295.
123. Ryan, L.,, R. Cotter,, W. Zink,, H. Gendelman, and, J. Zheng. 2002. Macrophages, chemokines and neuronal injury in HIV-1 associated dementia. Cell. Mol. Biol. 48: 137150.
124. Sacktor, N.,, M. McDermott,, K. Marder,, G. Schifitto,, O. Selnes,, J. McArthur,, Y. Stern,, S. Albert,, D. Palumbo,, K. Kieburtz,, J. De Marcaida,, B. Cohen, and, L. Epstein. 2002. HIV-associated cognitive impairment before and after the advent of combination therapy. J. Neurovirol. 8: 136142.
125. Sano, M.,, C. Ernesto,, R. Thomas,, M. Klauber,, K. Schafer,, M. Grundman,, P. Woodbury,, J. Growdon,, C. Cotman,, E. Pfeiffer,, L. Schneider, and, L. Thal. 1997. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N. Engl. J. Med. 336: 12161222.
126. Sappey, C.,, S. Legrand-Poels,, M. Best-Belpomme,, A. Favier,, B. Rentier, and, J. Piette. 1994. Stimulation of glutathione peroxidase activity decreases HIV type 1 activation after oxidative stress. AIDS 10: 14511461.
127. Sayed, M.,, and J. Eaton. 1992. Hemoglobin-induced oxidant damage to the central nervous system, p. 23–32. In M. Moslen and, C. Smith (ed.), Free Radical Mechanisms of Tissue Injury. CRC Press, Boca Raton, FL.
128. Schmidt, R.,, M. Hayn,, B. Reinhart,, G. Roob,, H. Schmidt,, M. Schumacher,, N. Watzinger, and, L. Launer. 1998. Plasma antioxidants and cognitive performance in middle-aged and older adults: results of the Austrian Stroke Prevention Study. J. Am. Geriatr. Soc. 46: 14071410.
129. Schreck, R.,, P. Rieber, and, P. Baeuerle. 1991. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kB transcription factor and HIV-1. EMBO J. 10: 2247.
130. Schwabe, J.,, and D. Rhodes. 1991. Beyond zinc fingers: steroid hormone receptors have a novel structural motif for DNA recognition. Trends Biochem. Sci. 16: 291.
131. Semba, R.,, N. Graham,, W. Caiaffa,, J. Margolick,, L. Clement, and, D. Vlahov. 1993. Increased mortality associated with vitamin A deficiency during human immunodeficiency virus type I infection. Arch. Intern. Med. 153: 21492154.
132. Sewell, M.,, K. Goggin,, J. Rabkin,, S. Ferrando,, M. McElhiney, and, S. Evans. 2000. Anxiety syndromes and symptoms among men with AIDS: a longitudinal controlled study. Psychosomatics 41: 294300.
133. Shi, B.,, J. Raina,, A. Lorenzo,, J. Busciglio, and, D. Gabuzda. 1998. Neuronal apoptosis induced by HIV-1 at protein and TNF-alpha: potentiation of neurotoxicity mediated by oxidative stress and implications for HIV-1 dementia. J. Neurovirol. 4: 281290.
134. Shor-Posner, G.,, and M. Baum. 1996. Nutritional alterations in HIV-1 seronegative drug users. Nutrition 12: 555556.
135. Shor-Posner, G.,, D. Feaster,, N. Blaney,, H. Rocca,, E. Mantero-Atienza,, J. Szapocznik,, C. Eisdorfer,, K. Goodkin, and, M. Baum. 1994. Impact of vitamin B6 status on psychological distress in a longitudinal study of HIV-1 infection. Int. J. Psychiatry Med. 24: 209222.
136. Shor-Posner, G.,, R. Lecusay,, M. Miguez,, G. Moreno-Black,, G. Zhang,, N. Rodriguez,, X. Burbano,, M. Baum, and, F. Wilkie. 2003. Psychological burden in the era of HAART: impact of selenium therapy. Int. J. Psychiatry Med. 33: 555569.
137. Shor-Posner, G.,, R. Lecusay,, G. Morales,, A. Campa, and, M. Miguez-Burbano. 2002. Neuroprotection in HIV-positive drug users: implications for antioxidant therapy. J. Acquir. Immune Defic. Syndr. 31: S84S88.
138. Shor-Posner, G.,, R. Morgan,, F. Wilkie,, C. Eisdorfer, and, M. Baum. 1995. Plasma cobalamin levels affect information processing speed in a longitudinal study of HIV-1 disease. Arch. Neurol. 52: 195198.
139. Shukla, A.,, M. Dikshit, and, R. Srimal. 1995. Status of antioxidants in brain microvessels of monkey and rat. Free Radic. Res. 22: 303308.
140. Skurnick, J.,, J. Bogden,, H. Baker,, F. Kemp,, A. Sheffet,, G. Qualtrone, and, D. Louria. 1996. Micronutrient profiles in HIV-1-infected heterosexual adults. J. Acquir. Immune Defic. Syndr. 12: 7583.
141. Smith, C.,, J. Carney,, P. Starke-Reed,, C. Oliver,, E. Stadtman,, R. Floyd, and, W. Markesbery. 1991. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc. Natl. Acad. Sci. USA 88: 15401543.
142. Smith, M.,, G. Perry,, P. Richey,, L. Sayre,, V. Anderson,, M. Beal, and, N. Jowall. 1996. Oxidative damage in Alzheimer’s. Nature 382: 120121.
143. Smits, H.,, L. Boven,, C. Pereira,, J. Verhoef, and, H. Nottet. 2001. Role of macrophage activation in the pathogenesis of Alzheimer’s disease and human immunodeficiency virus type 1-associated dementia. Eur. J. Clin. Investig. 30: 526535.
144. Staal, F.,, M. Roederer,, L. Herzenberg, and, L. Herzenberg. 1990. Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. Proc. Natl. Acad. Sci. USA 87: 9943.
145. Stephenson, C. B.,, G. S. Marquis,, S. D. Douglas,, L. A. Kruzich, and, C. M. Wilson. 2007. Glutathione, glutathione peroxidase, and selenium status in HIV-positive and HIV-negative adolescents and young adults. Am. J. Clin. Nutr. 85: 173181.
146. Stoeck, M.,, W. Kromer, and, V. Gekeler. 1998. Induction of IL-15 mRNA and protein in A549 cells by pro-inflammatory cytokines. Immunobiology 199: 1422.
147. Takeda, A. 2004. Essential trace metals and brain function. Yakugaku Zasshi 124: 577585.
148. Tanala, Y.,, S. Shiozawa,, I. Morito, and, T. Fujita. 1990. Role of zinc in interleukin 2 mediated T-cell activation. Scand. J. Immunol. 31: 547.
149. Tang, A.,, N. Graham,, R. Semba, and, A. Saah. 1997. Association between serum vitamin A and E levels and HIV-1 disease progression. AIDS 11: 613620.
150. Tang, A.,, J. Lanzillotti,, K. Hendricks,, J. Gerrior,, M. Ghosh,, M. Woods, and, C. Wanke. 2005. Micronutrients: current issues for HIV care providers. AIDS 19: 847861.
151. Tang, A.,, and E. Smit. 2000. Oxidative stress in HIV-1-infected injection drug users. J. Acquir. Immune Defic. Syndr. 25: S12S18.
152. Tucker, D., and H. Sandstead. 1984. Neuropsychological function in experimental zinc deficiency in humans, p. 139–152. In C. Frederickson,, G. Howell, and, E. Kasarskis (ed.), The Neurobiology of Zinc. Part B. Deficiency, Toxicity and Pathology. Alan R. Liss, New York, NY.
153. Tully, C.,, D. Snowdon, and, W. Markesbery. 1995. Serum zinc, senile plaques and neurofibrillary tangles: findings from the Nun Study. Neuroreport 6: 21052108.
154. Turchan, J.,, C. Pocernich,, C. Gairola,, A. Chauhan,, G. Schifitto,, D. Butterfield,, S. Buch,, O. Narayan,, A. Sinai,, J. Geiger, J. Berger,, H. Elford, and, A. Nath. 2003a. Oxidative stress in HIV demented patients and protection ex vivo with novel antioxidants. Neurology 60: 307314.
155. Turchan, J.,, N. Sacktor,, V. Wojna,, K. Conant, and, A. Nath. 2003b. Neuroprotective therapy for HIV dementia. Curr. HIV Res. 1: 373383.
156. Verbanck, P.,, and L. Oliver. 1991. Changing psychiatric symptoms in a patient with vitamin B12 deficiency. J. Clin. Psychiatry 52: 182183.
157. Wanke, C.,, M. Silva,, T. Knox,, J. Forrester,, D. Spiegelman, and, S. Gorbach. 2000. Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin. Infect. Dis. 31: 803805.
158. Wefers, H.,, and H. Seis. 1988. The protection by ascorbate and glutathione against lipid peroxidation is dependent on vitamin E. Eur. J. Biochem. 174: 353357.
159. Whitney, E.,, and S. Rolfes. 1999. Understanding Nutrition, 8th ed., p. 290435. West/Wadsworth, Belmont, CA.
160. Wilkie, F.,, R. Goodkin,, R. Morgan,, D. Feaster,, M. Fletcher,, N. Blaney,, M. Baum,, J. Szapocznik, and, C. Eisdorfer. 1998. Mild cognitive impairment and risk of mortality in HIV-1 infection. J. Neuropsychiatry Clin. Neurosci. 10: 125132.
161. Woods, M. N.,, A. M. Tang,, J. Forrester,, C. Jones,, K. Hendricks,, B. Ding, and, T. A. Knox. 2003. Effect of dietary intake and protease inhibitors on serum vitamin B12 levels in a cohort of human immunodeficiency virus-positive patients. Clin. Infect. Dis. 37: 124131.
162. Yost, H.,, and E. Kligman. 2001. Nutritional modulation of neurodegenerative disorders, p. 333–341. In R. Watson (ed.), Handbook of Nutrition in the Aged, 3rd ed. CRC Press, Boca Raton, FL.
163. Zhang, Z.,, P. Inserra,, B. Liang, and, R. Watson. 1998. Antioxidants and AIDS, p. 179–192. In R. Watson (ed.), Nutrients and Foods in AIDS. CRC Press, Boca Raton, FL.
164. Zinkernagel, C.,, P. Taffe,, M. Rickenbach,, R. Amiet,, B. Ledergerber,, A. Volkart,, U. Rauchfleisch,, A. Kiss,, V. Werder,, P. Vernazza,, M. Battegay, and Swiss HIV Cohort Study. 2001. Importance of mental health assessment in HIV-infected outpatients. J. Acquir. Immune Defic. Syndr. 28: 240249.
165. Zucker, D.,, R. Livingston,, R. Nakra, and, P. Clayton. 1981. B12 deficiency and psychiatric disorders: case report and literature review. Biol. Psychiatry 16: 197205.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error