Journal of NeuroVirology

, Volume 15, Issue 3, pp 257–274

Human immunodeficiency virus type 1 in the central nervous system leads to decreased dopamine in different regions of postmortem human brains

  • Adarsh M. Kumar
  • J. B. Fernandez
  • Elyse J. Singer
  • Deborah Commins
  • Drenna Waldrop-Valverde
  • Raymond L. Ownby
  • Mahendra Kumar
Article

Abstract

Human immunodeficiency virus type 1 (HIV-1) invades the central nervous system (CNS) shortly after infection and becomes localized in varying concentrations in different brain regions, the most vulnerable is the basal ganglia (BG). It is hypothesized that HIV-1-mediated neuropathogenesis involves degeneration of dopaminergic neurons in the substantia nigra and the loss of dopaminergic terminals in the BG, leading to deficits in the central dopaminergic activity, resulting in progressive impairment of neurocognitive and motor functions. In the era of highly active antiretroviral therapy (HAART), although the incidence of HIV-associated dementia (HAD) has decreased, the neurocognitive and neuropsychological deficits continue to persist after HAART. In this study, We investigated the impact of HIV-1 on dopaminergic activity with respect to concentrations of dopamine (DA) and homovanillic acid (HVA) in different regions of postmortem human brains of HIV-1negative and HIV-1+ individuals and their relationship to neurocognitive impairment. We found that in HIV-1+ as well as HIV-negative cases, dopamine and HVA concentrationsin ranged widely in different brain regions. In HIV-negative brain regions, the highest concentration of DA was found in putamen, caudate, substantia nigra, and the basal ganglia. In HIV-1+ cases, there was a significant decrease in DA levels in caudate nucleus, putamen, globus pallidus, and substantia nigra compared to that in HIV-negative cases. In HIV-1+ cases, a strong correlation was found between DA levels in substantia nigra and other brain regions. Concentration of HVA in HIV-negative cases was also highest in the regions containing high dopamine levels. However, no significant decrease in regional HVA levels was found in HIV-1+ cases. HIV-1 RNA load (nondetectable [ND] to log10 6.9 copies/g tissue) also ranged widely in the same brain regions of HIV-1+ cases. Interestingly, the brain regions having the highest HIV-1 RNA had the maximum decrease in DA levels. Age, gender, ethnicity, and postmortem interval were not correlated with decrease in DA levels. Profile of DA, HVA, and HIV-1 RNA levels in the brain regions of HIV-1+ individuals treated with HAART was similar to those not treated with HAART. A majority of HIV-1+ individuals had variable degrees of neurocognitive impairments, but no specific relationship was found between the regional DA content and severity of neurocognitive deficits. These findings suggest widespread deficits in dopamine in different brain regions of HIV-1-infected cases, and that these deficits may be the results of HIV-1-induced neurodegeneration in the subcortical regions of human brain.

Keywords

CNS dopamine HIV-1 HVA 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Achim CL, Heyes MP, Wiley C (1993). Quantitation of human immunodeficiency virus immune activation factors, and quinolininc acid in AIDS brains. J Clin Invest 91: 2769–2775.CrossRefPubMedGoogle Scholar
  2. Adolfsson R, Gottfries CG, Roos BE, Winblad B (1979). Post-mortem distribution of dopamine and homovanillic acid in human brain, variations related with age, and a review of literature. J Neurol Transm 45: 81–105.CrossRefGoogle Scholar
  3. Ances BM, Roc AC, Wang J, Korczkowski M, Okawa J, Stern J, Kim J, Wolf R, Lawler K, Kolson DL, Detre JA (2006). Caudate blood flow and volume are reduced in HIV+ neurocognitively impaired patients. Neurology 66: 862–866.CrossRefPubMedGoogle Scholar
  4. Ances BM, Ellis RJ (2007). Dementia and neurocognitive disorders due to HIV-1 infection. Semin Neurol 27: 86–92.CrossRefPubMedGoogle Scholar
  5. Anthony IC, Ramage SN, Carnie FW, Simmonds P, Bell JE (2005). Influence of HAART on HIV-related CNS disease and neuroinflammation. J Neuropathol Exp Neurol 64: 529–536.PubMedGoogle Scholar
  6. Arai H, Kosaka K, Lizuka R (1984). Changes in biogenic amines and their metabolites in postmortem brains from patients with Alzheimer-type dementia. J Neurochem 43: 388–393.CrossRefPubMedGoogle Scholar
  7. Aylward EH, Henderer JD, McArthur JC, Brettschneider PD, Harris GJ, Barta PE, et al (1993). Reduced basal ganglia volume in HIV-1-associated dementia: results from quantitative neuroimaging. Neurology 43: 2099–2104.PubMedGoogle Scholar
  8. Bagasra O, Levi E, Bobroski L (1996). Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 10: 573–585.CrossRefPubMedGoogle Scholar
  9. Banks WA, Robinson SM, Wolf KM, Bess JW Jr, Arthur LO (2004). Binding, internalization, and membrane incorporation of human immunodeficiency virus-1 at the blood-brain barrier is differentially regulated. Neuroscience 128: 143–153.CrossRefPubMedGoogle Scholar
  10. Bennet BA, Rusyniak DE, Hollingsworth CK (1995). HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures. Brain Res 705: 168–176.CrossRefGoogle Scholar
  11. Berger JR, Kumar M, Kumar A, Fernandez JB, Levine B (1994). Cerebrospinal fluid dopamine in HIV-1 infection. AIDS. 8: 67–71.CrossRefPubMedGoogle Scholar
  12. Berger JR, Nath A (1997). HIV dementia and the basal ganglia. Intervirology 40: 122–131.CrossRefPubMedGoogle Scholar
  13. Berger JR, Arendt G (2000). HIV-dementia: the role of the basal ganglia and dopaminergic systems. J Psychopharmacol 14: 214–221.CrossRefPubMedGoogle Scholar
  14. Bobardt MD, Salmon P, Wang L, Esko JD, Gabzuda D, Fiala M, Trono D, Van der Schueren B, David G, Gallay PA (2004). Contribution of proteoglycans to human immunodeficiency virus type 1 brain invasion. J Virol 78: 6567–6584.CrossRefPubMedGoogle Scholar
  15. Brew BJ (1993). HIV-1 related neurological disease. J Acquired Immune Defic Syndr 6(Suppl 1): S10-S15.Google Scholar
  16. Broder CC, Dimitrov DS (1996). HIV and the 7-transmembrane domain receptors. Pathobiology 64: 171–179.CrossRefPubMedGoogle Scholar
  17. Castello JMB, Courtney MG, Melrose RJ, Stern CE (2007). Putamen hypertrophy in nondemented patients with human immunodeficiency virus infection and cognitive compromise. Arch Neurol 64: 1275–1280.CrossRefGoogle Scholar
  18. Carlsson A, Winblad B (1976). Influence of age and time interval between death and autopsy on dopamine and 3methoxytyramine levels in human basal ganglia. J Neural Transm 38: 271–276.CrossRefPubMedGoogle Scholar
  19. Chang L, Ernst T, Leonido-Yee M, Witt M, Speck O, Walot I, Miller EN (1999). Highly active antiretroviral therapy reverses brain metabolite abnormalities in mild HIV dementia. Neurology 53: 782–789.PubMedGoogle Scholar
  20. Chang L, Lee PL, Yiannoutsos CT, Ernst T, Marra CM, Richards T, Kolson D, Schifitti G, Jarvik JG, Miller EN, Lenkinski R, Gonzalez G, Navia BA (2004). A multicenter in vivo protons-MRS study of HIV-associated dementia and its relationship to age. Neuroimage 23: 1336–1347.CrossRefPubMedGoogle Scholar
  21. Choe H, Farzan M, Sun Y, Sullivan N, Rollins B, Ponath PD, Wu L, Mackay CR, LaRosa G, Newman W, Gerard N, Gerard C, Sodroski J (1996). The β-chemokine receptors CCR3 and CCR5 facilitate infection by primary HIV-1 isolates. Cell 85: 1135–1148.CrossRefPubMedGoogle Scholar
  22. Danna Consortium (1998). A randomized double blind placebo controlled trial of deprenyl and thioctic acid in human immunodeficiency virus-associated cognitive impairment. Danna Consortium on the therapy of HIV-dementia and related cognitive disorders. Neurology 50: 645–651.Google Scholar
  23. Dore GJ, McDonald A, Li Y, Kaldor JM, Brew BJ (2003). Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 17: 1539–1545.CrossRefPubMedGoogle Scholar
  24. Eden A, Price RW, Spudich S, Fuchs L, Hargberg L, Gisslen M (2007). Immune activation of the central nervous system is still present after >4 years of effective highly active antiretroviral therapy. J Infect Dis 196: 1779–1783.CrossRefPubMedGoogle Scholar
  25. Ellis R Childers ME Kumar AM Kumar M Goetz T Caligiuri M (2004). Decreased cerebrospinal fluid dopamine correlates with impaired motor skills in HIV-1 infection and methamphetamine dependence. Presented at the Society for Neuroscience, 34th Annual Meeting, San Diego, Oct 23–27.Google Scholar
  26. Fillipi CG, Sze G, Farber SJ, Shahmanesh M, Selwyn PA (1998). Regression of HIV encelopathy and basal ganglia signal intensity abnormality at MR imaging in patients with AIDS after the initiation of protease inhibitor therapy. Radiology 206: 491–498.Google Scholar
  27. Ensoli F, Wang H, Fiorelli V, Zeichner SL, Cristofero De MR, Luzi G, Thiele CJ (1997). HIV-1 infection and the developing nervous system: lineage-specific regulation of viral gene expression and replication in distinct neuronal precursors. J NeuroVirol 3: 290–298.CrossRefPubMedGoogle Scholar
  28. Garris PA, Ciolkowski EL, Pastore P, Weightman RM (1994). Efflux of dopamine from the synaptic cleft in the nucleus accumbence of the rat brain. J Neurosci 14: 6084–6093.PubMedGoogle Scholar
  29. Georgiou FM, Gonenc A, Waldrop-Valverde D, Kuker RA, Ezzuddin SH, Sfakianakis GN, Kumar M (2008). Analysis of the effect of injecting drug use and HIV-1 infection on 18F-FDG PET brain metabolism. J Nucl Med 49: 1999–2005.CrossRefPubMedGoogle Scholar
  30. Gisslen M, Larsson M, Norkrans G, Fuchs D, Wachter H, Hagberg L (1994). Tryptophan concentrations increase in cerebrospinal fluid and blood after zidvudine treatment in patients with HIV type 1 infection. AIDS Res Hum Retroviruses 10: 947–951.CrossRefPubMedGoogle Scholar
  31. Glass JD, Fedor H, Wesselingh SL, McArthur JC (1995). Immunocytochemical quantification of human immunodeficiency virus in the brain: correlations with dementia. Ann Neurol 38: 755–762.CrossRefPubMedGoogle Scholar
  32. Gray F, Adle-Biassette H, Chreien F, Lorin de la Grandmaison G, Force G, Keohane C (2001). Neuropatholoy and neurodegeneration in human immunodeficiency virus infection. Pathogenesis of HIV-induced lesion of the brain, correlations with HIV-associated disorders and modifications according to treatments. Clin Neuropathol 20: 146–155.PubMedGoogle Scholar
  33. Harrison MIJ, Newman SP, Hall-Craggs MA, et al (1998). Evidence of CNS impairment in HIV-1 infection: clinical, neuropsychological, EEG, and MRI/MNRS study. J Neurosurg Psychiatr 5: 301–307.CrossRefGoogle Scholar
  34. Herregodts P, Ebinger G, Michotte Y (1991). Distribution of monoamines in human brain: evidence for neurochemical heterogeneity in subcortical as well as cortical areas. Brain Res 542: 300–306.CrossRefPubMedGoogle Scholar
  35. Heyes MP, Saito K, Markey SP (1992). Human macrophages convert l-tryptophan in to the neurotoxin quinolininc acid. Biochem J 283: 633–635.PubMedGoogle Scholar
  36. Hinkin CH, Castellon SA, Hardy DJ, Farinpour R, Newton J, Singer E (2001). Methylphenidate improves HIV-associated cognitive slowing. J Neuropsychiatry Clin Neurosci 13: 248–254.PubMedGoogle Scholar
  37. Ho D, Rota TR, Schooley RT, Kaplan JC, Allan JD, Groopman JE, et al (1985). Isolation of HTLV-III from cerebrospinal fluid and neural tissues of patients with neurologic syndromes related to the acquired immunodeficiency syndrome. N Eng J Med 313: 1493–1497.CrossRefGoogle Scholar
  38. Hriso E, Kuhn T, Masdeu JC, Grundman M (1991). Extrapyramidal symptoms due to dopamine-blocking agents in patients with AIDS encephalopathy. Am J Psychiatry 11: 1558–156.Google Scholar
  39. Itoh K, Mehraein P, Weis S (2000). Neuronal damage of the substantia nigra in HIV-infected brains. Acta Neuropathol 99: 376–384.CrossRefPubMedGoogle Scholar
  40. Jernigan TL, Archibald S, Hesselink JR (1993). Magnetic resonance imaging morphometric analysis of cerebral volume loss in human deficiency virus infection. Arch Neurol 50: 250–255.PubMedGoogle Scholar
  41. Johnson RT, Glass JD, McArthur JC, Chesebro BW (1996). Quantitation of human deficiency virus in brains of demented and non-demented patients with acquired immunodeficiency syndrome. Ann Neurol 39: 392–395.CrossRefPubMedGoogle Scholar
  42. Kaul M, Ma Q, Medders KE, Desai MK, Lipton SA (2007). HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death Differ 14: 296–305.CrossRefPubMedGoogle Scholar
  43. Kieburtz KD, Epstein LG, Gelbard HA, Greenamyre JT (1991). Excitotoxicity and dopaminergic dysfunction in the acquired immunodeficiency syndrome dementia complex. Therapeutic implications. Arch Neurol 48: 1281–1284.PubMedGoogle Scholar
  44. Kieburtz KD, Ketonen L, Cox C, Grossman H, Holloway R, Booth H, Hickey C, Feigin A, Caine D (1996). Cognitive performance and regional brain volume in human immunodeficiency virus type 1 infection. Arch Neurol 53: 155–158.PubMedGoogle Scholar
  45. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJJ, Roden DM (1998). The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 101: 289–294.CrossRefPubMedGoogle Scholar
  46. Koutsillieri E, Sopper S, Scheller C, ter Meulen V, Riederer P (2002). Parkinson in HIV dementia. J Neural Transm 109: 767–775.CrossRefGoogle Scholar
  47. Kumar AM, Berger JR, Eisdorfer C, Fernandez JB, Goodkin K, Kumar M (2001). Cerebrospinal fluid 5-hydroxy-tryptamine and 5-hydroxyindoleacetic acid in HIV-1 infection. Neuropsychobiology 44: 13–18.CrossRefPubMedGoogle Scholar
  48. Kumar AM, Borodowsky I, Fernandez JB, Gonzalez L, Kumar M (2007). Human immunodeficiency virus type 1 RNA levels in different brain regions of human brain: quanyification using real-time reverse transcriptase-polymerase chain reaction. J NeuroVirol 13: 210–224.CrossRefPubMedGoogle Scholar
  49. Kumar AM, Fernandez JB, Antoni MH, Eisdorfer S, Kumar M (2003). Catecholamines quantification in body fluids using isocratic, reverse phase HPLC-CoulArray multi-electrode chemical detector system: Investigation of sensitivity, stability, and reproducibility. J Liquid Chromatogr Relat Technol 26: 3433–3451.CrossRefGoogle Scholar
  50. Kumar AM, Fernandez JB, Gonzalez L, Kumar M (2006). Ultramicro quantification of dopamine and homovanillic acid in human brain tissue: quest for higher recovery and sensitivity with CoulArray HPLC-ECD system. J Liquid Chromatogr Relat Technol 29: 777–799.CrossRefGoogle Scholar
  51. Kure K, Weidenheim KM, Lyman WD, Dickson DW (1990). Morphology and distribution of HIV-1 gp41-positive microgila in subacute AIDS encephalitis: pattern of involvement resembling a multisystem degeneration. Acta Neuropahol (Berl) 80: 393–400.CrossRefGoogle Scholar
  52. Larsson M, Hagberg L, Forsman A, Norkrans G (1991). Cerebrospinal fluid catecholamine metabolites in HIV-1 infected patients. J Neurosci Res 28: 406–409.CrossRefPubMedGoogle Scholar
  53. Lopez OL, Smith G, Meltzer CC, Becker JT (1999). Dopamine systems in human immunodeficiency virus-associated dementia [review]. Neuropsychiatry Neuropsychol Behav Neurol 12: 184–192.PubMedGoogle Scholar
  54. Mackay AVP, Yates CM, Wright A, Hamilton P, Davies P (1986). Regional distribution of monoamines and their metabolites in the human brain. J Neurochem 65: 135–153.Google Scholar
  55. Magyar R (1993). Pharmacology of monoamine oxidase type B inhibitors. In: Inhibitors of monoamine oxidase B, pharmacology and clinical use in neurodegenerative disorders. Szelenyi I. Basel, Switzerland: Birkhauser, pp 125–143.Google Scholar
  56. Masliah E, Achim CL, Ge N, DeTeresa R, Terry D, Wiley CA (1992). Spectrum of HIV associated neocortical damage. Ann Neurol 32: 85–93.CrossRefGoogle Scholar
  57. Maslin CLV, Kedzierska K, Webseter N, Muller W, Crowe S (2005). Transendothelial migration of monocytes: the underlying molecular mechanisms and consequences of HIV-1 infection. Curr HIV Res 3: 303–317.CrossRefPubMedGoogle Scholar
  58. Mattson MP, Haughey NJ, Nath A (2005). Cell death in HIV dementia [review]. Cell Death Differ 12(Suppl 1): 893–904.CrossRefPubMedGoogle Scholar
  59. Merril JE, Chen ISV (1991). HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB J 5: 2391–2397.Google Scholar
  60. Mirsattari SM, Power C, Nath A (1998). Parkinsonism with HIV infection. Movement Disord 13: 684–689.CrossRefPubMedGoogle Scholar
  61. Morgello S, Gelman BB, Kozlowski PB, Vinters HV, Masliah E, Cornford M, Cavert W, Marra C, Grant I, Singer EJ (2001). The National NeuroAIDS Tissue Consortium: a new paradigm in brain banking with an emphasis on infectious diseases. Neuropathol Appl Neurobiol 27: 326–335.CrossRefPubMedGoogle Scholar
  62. Morgenson GJ, Yang CR (1991). The contribution of basal forebrain to limbic-motor integration and the mediation of motivation to action. Adv Exp Med Biol 295: 267–273.Google Scholar
  63. Nath A (2002). Human immunodeficiency virus (HIV) proteins in neuropathogenesis of HIV dementia. J Infect Dis 186(Suppl 2): S193-S198.CrossRefPubMedGoogle Scholar
  64. Nath A, Anderson C, Jones M, Maragose W, Booz R, Mactutus C, Bell J, Hauser K, Mattson M (2000). Neurotoxicity and dysfunction of dopaminergic systems associated with AIDS dementia. J Psychopharmacol 14: 222–227.CrossRefPubMedGoogle Scholar
  65. Nath A, Sacktor N (2006). Influence of highly active antiretroviral therapy on persistence of HIV in the central nervous system. Curr Opin Neurol 19: 358–361.CrossRefPubMedGoogle Scholar
  66. Navia BA, Price RW (1987). The acquired immune deficiency syndrome dementia complex as the presenting or sole manifestation of human immune deficiency virus infection. Arch Neurol 44: 65–69.PubMedGoogle Scholar
  67. Nottet HS, Persidsky Y, Sasseville VG, Nukuna AN, Bock P, Zhai QH, Sharer LR, McComb RD, Swindells S, Soderland C, Gendelman HE (1996). Mechanisms for the transendothelial migration of HIV-1 infected monocytes in to the brain. J Immunol 156: 1284–1295.PubMedGoogle Scholar
  68. Parra A, Ramirez-Peredo J, Larrea F, Cabrera V, Coutino B, Torres I, Angeles A, Perez-Romano B, Ruiz-Arguelles G, Ruiz-Arguelles A (2001). Decreased dopaminergic tone and increased basal bioactive prolactin in men with human immunodeficiency virus infection. Clin Endocrinol 54: 731–738.CrossRefGoogle Scholar
  69. Persidsky Y, Gendelman HE (2003). Mononuclear phagocyte immunity and the neuropathogenesis of HIV-1 infection. J Leuk Biol 74: 691–701.CrossRefGoogle Scholar
  70. Persidsky Y, Stins M, Way D, Witte MH, Weinand M, Kim KS, Bock P, Gendelman HE, Fiala M (1997). A model for monocyte migration through the blood brain barrier during HIV-1 encephalitis. J Immunol 158: 3499–3510.PubMedGoogle Scholar
  71. Price RW, Brew BJ (1988). The AIDS dementia complex. J Infect Dis 158: 1079–1083.PubMedGoogle Scholar
  72. Ranki A, Nyberg M, Ovod V, Haltia M, Elovaara I, Raininko R, Haapasalo H, Krohn K (1995). Abundant expression of HIV Nef and Rev proteins in brain astrocytes in vivo is associated with dementia. AIDS 9: 1001–1008.CrossRefPubMedGoogle Scholar
  73. Resnick L, Berger JR, Shapshak P, Tourtellotte WW (1988). Early penetration of the blood brain barrier by HIV. Neurology 38: 9–14.PubMedGoogle Scholar
  74. Reyes MG, Faraldi F, Senseng CS, Flowers C, Fariello R (1991). Nigral degeneration in acquired immunodeficiency syndrome (AIDS). Acta Neuropathol 82: 39–44.CrossRefPubMedGoogle Scholar
  75. Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ (2007). The prevalence of incidence of neurocognitive impairment in the HAART era. AIDS 21: 1915–1921.CrossRefPubMedGoogle Scholar
  76. Rottenberg DA, Sidtis JJ, Strother SC, Schaper KA, Anderson JR, Nelson MJ, et al (1996). Abnormal cerebral glucose metabolism in HIV-1 seropositive subjects with and without dementia. J Nucl Med 37: 1133–1141.PubMedGoogle Scholar
  77. Sacktor N, McDermott MP, Marder K, Schiffito G, Selnes OA, McArthur JC, Stern Y, Albert S, Palumbo D, Kieburtz K, De Marcaida JA, Cohen B, Epstein L (2002). HIV-associated cognitive impairment before and after the advent of combination therapy. J NeuroVirol 8: 136–142.CrossRefPubMedGoogle Scholar
  78. Sacktor N, Schiffito G, McDermott MP, Marder K, McArthur JC, Kieburtz K (2000). Transdermal selegeline in HIV-associated cognitive impairment. Pilot, placebo controlled study. Neurology 54: 233–235.PubMedGoogle Scholar
  79. Sardar AM, Czudek C, Reynolds GP (1996). Dopamine deficits in the brain: The neurochemical basis of Parkinsonian symptoms in AIDS. Neuroreport 7: 910–912.CrossRefPubMedGoogle Scholar
  80. Scheller C, Sopper S, Jenuwein M, Neuen-Jacob E, Tatschner T, Grunblatt E, ter Meulen V, Riederer P, Koutsilieri E (2005). Early impairment in dopaminergic neurotransmission in brains of SIV-infected rhesus monkey due to microglia activation. J Neurochem 95: 377–387.CrossRefPubMedGoogle Scholar
  81. Schrager LK, D’Souza MP (1998). Cellular and anatomical reservoirs of HIV-1 in patients receiving potent antiretroviral combination therapy. JAMA 280: 67–71.CrossRefPubMedGoogle Scholar
  82. Spokes EGS (1979). An analysis of factors influencing measurements of dopamine, noradrenaline, glutamate decarboxylase and cholineacetylase in human postmortem brain tissue. Brain 102: 333–346.CrossRefPubMedGoogle Scholar
  83. Stout JC, Ellis RJ, Jernigan TL, et al (1998). HIV Neurobehavioral Research Center Group. Progressive cerebral volume loss in human deficiency virus infection: a longitudinal volumetric magnetic resonance imaging study. Arch Neurol 55: 161–168.CrossRefPubMedGoogle Scholar
  84. Taylor M, Schweinsberg BC, Alhassoon OM, Gangavatana A, Brown GG, Young-Casey C, Letendre SL Grant I the HNRC group (2007). Effects of human immunodeficiency virus and methamphetamine on cerebral metabolites measured with magnetic resonance spectroscopy. J NeuroVirol 13: 150–159.CrossRefPubMedGoogle Scholar
  85. Tozzi V, Balestra P, Murri R, Galgani S, Bellagamba R, Narciso P, Antonori A, Giulianelli M, Tosi G, Fantoni M, Sampaolesi A, Noto P, Ippolito G, Wu AW (2004). Neurocognitive impairment influences quality of life in HIV-infected patients receiving HAART. Int J STD AIDS 15: 254–259.CrossRefPubMedGoogle Scholar
  86. Tozzi V, Balestra P, Bellagamba R, Corpolongo A, Salvatori MF, Visco-Comandini U, Vlassi C, Giulianelli M, Galgani S, Antinore A, Narciso P (2007). Persistence of neuropsychological deficits despite long-term highly active antiretroviral therapy in patients with HIV-related neurocognitive impairment: prevalence and risk factors. J Acquir Immune Defic Syndr 45: 174–182.CrossRefPubMedGoogle Scholar
  87. Volkow N, Fowler J, Gately S, Logan J, Wang G, Ding Y et al (1996). PET evaluation of the dopamine system of the human brain. J Nucl Med 37: 1242–1256.PubMedGoogle Scholar
  88. Von Giesen HJ, Ittsack HJ, Wenserski F, Koller H, Hefter H, Arendt G (2001). Basal ganglia metabolite abnormalities in minor motor disorders associated with human immunodeficiency virus type 1. Arch Neurol 58: 1281–1286.CrossRefGoogle Scholar
  89. Wang GJ, Chang L, Volkow ND, Telang F, Logan J, Ernst T, Fowler JS (2004). Decreased brain dopaminergic transporters in HIV-1 associated dementia patients. Brain 127: 2452–2458.CrossRefPubMedGoogle Scholar
  90. Wester P, Bergstrom U, Erikson A, Gezelius C, Hardy J, Winblad B (1990). Ventricular cerebrospinal fluid monoamine transmitters and metabolite concentrations reflect human brain neurochemistry in autopsy cases. J Neurochem 54: 1148–1156.CrossRefPubMedGoogle Scholar
  91. WHO/UNAIDS Agency (2007). AIDS Epidemic Update, November, 2007.Google Scholar
  92. Wiley CA, Soontornniyomkij V, Radhakrishnan L, Masliah E, Mellors J, Herman SA, Dalley P, Achim CL (1998). Distribution of brain HIV load in AIDS. Brain Pathol 8: 277–284.CrossRefPubMedGoogle Scholar
  93. Wiley CA, Shrie RD, Nelson JA, Lampert PW, Oldstone MB (1986). Cellular localization of human immunodeficiency virus infection within the brains of acquired immunodeficiency syndrome patients. Proc Natl Acad Sci USA 83: 7089–7093.CrossRefPubMedGoogle Scholar
  94. Zauli G, Secchiero P, Luigi R, Gibellini D, Mirandola P, Mazzoni M, Milani MD, Dowd DR, Capitani S, Vitale M (2000). HIV-1 Tat-mediated inhibition of the tyrosine hydroxylase gene expression in dopaminergic neuronal cells. JBiol Chem 275: 4159–416.CrossRefGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2009

Authors and Affiliations

  • Adarsh M. Kumar
    • 1
  • J. B. Fernandez
    • 1
  • Elyse J. Singer
    • 2
  • Deborah Commins
    • 3
  • Drenna Waldrop-Valverde
    • 1
  • Raymond L. Ownby
    • 1
  • Mahendra Kumar
    • 1
  1. 1.Department of Psychiatry and Behavioral SciencesUniversity of Miami Miller School of Medicine (D-21)MiamiUSA
  2. 2.Department of neurologyUniversity of CaliforniaLos AngelesUSA
  3. 3.Keck School of MedicineUniversity of Southern CaliforniaLos AngelesUSA

Personalised recommendations