Journal of NeuroVirology

, Volume 10, Issue 2, pp 109–115

The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus encephalitis: Deficits in cognitive function

  • William C. Griffin
  • Lawrence D. Middaugh
  • Jennifer E. Cook
  • William R. Tyor
Article

Abstract

The severe combined immunodeficient (SCID) mouse model of human immunodeficiency virus (HIV) encephalitis exhibits many of the histopathological and pathophysiological features of human HIV-associated dementia (HAD). Although deficits that may resemble HAD in humans have been reported for HIV-infected SCID mice, the cognitive deficit aspect of the model has very limited empirical support. Here, the authors report that HIV-infected SCID mice display cognitive deficits on a task requiring the animal to learn and remember the spatial relationship of cues in its environment in order to locate a submerged platform in a Morris water maze. The cognitive deficits manifest as longer latencies to locate the platform on the last day of the maze acquisition period and during a retention test 8 days later. Control experiments indicated that the poor performance by HIV-infected mice in comparison to controls was not due to impaired motor function or swimming ability, impaired visual acuity, or increased susceptibility to fatigue. Thus, the increased times required for HIV-infected mice to locate the submerged platform during the acquisition and memory tests likely reflect a cognitive deficit, rather than sensorimotor or emotional abnormalities. These behavioral deficits are associated with significant increases in astrogliosis and microgliosis in the HIV-infected mice. The results of this study strengthen the SCID mouse model of HIV encephalitis by definitively establishing cognitive deficits for the model in addition to its previously reported neuropathological features.

Keywords

AIDS animal model dementia HIV-associated dementia HIV encephalitis SCID 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderson ER, Boyle J, Zink WE, Persidsky Y, Gendelman HE, Xiong H (2003). Hippocampal synaptic dysfunction in a murine model of human immunodeficiency virus type 1 encephalitis. Neuroscience 118: 359–369.CrossRefPubMedGoogle Scholar
  2. Astur RS, Taylor LB, Mamelak AN, Philpott L, Sutherland RJ (2002). Humans with hippocampus damage display severe spatial memory impairments in a virtual Morris water task. Behav Brain Res 132: 77–84.CrossRefPubMedGoogle Scholar
  3. Avgeropoulos N, Kelley B, Middaugh L, Arrigo S, Persidsky Y, Gendelman HE, Tyor WR (1998). SCID mice with HIV encephalitis develop behavioral abnormalities. J Acquir Immune Defic Syndr Hum Retrovirol 18: 13–20.PubMedGoogle Scholar
  4. Carman HM, Mactutus CF (2001). Ontogeny of spatial navigation in rats: a role for response requirements? Behav Neurosci 115: 870–879.CrossRefPubMedGoogle Scholar
  5. D’Hooge R, De Deyn PP (2001). Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36: 60–90.CrossRefPubMedGoogle Scholar
  6. Inman-Wood SL, Williams MT, Morford LL, Vorhees CV (2000). Effects of prenatal cocaine on Morris and Barnes maze tests of spatial learning and memory in the offspring of C57BL/6J mice. Neurotoxicol Teratol 22: 547–557.CrossRefPubMedGoogle Scholar
  7. Masliah E, Ge N, Achim CL, Hansen LA, Wiley CA (1992). Selective neuronal vulnerability in HIV encephalitis. J Neuropathol Exp Neurol 51: 585–593.CrossRefPubMedGoogle Scholar
  8. McArthur J (1990). Neurologic disease associated with HIV-1 infection. In: Current therapy in neurologic disease-3. Johnson RT (ed). New York: Decker, pp 124–129.Google Scholar
  9. McArthur JC, Haughey N, Gartner S, Conant K, Pardo C, Nath A, Sacktor N (2003). Human immunodeficiency virus-associated dementia: an evolving disease. J NeuroVirol 9: 205–221.PubMedGoogle Scholar
  10. McArthur JC, Hoover DR, Bacellar H, Miller EN, Cohen BA, Becker JT, Graham NM, McArthur JH, Selnes OA, Jacobson LP (1993). Dementia in AIDS patients: incidence and risk factors. Multicenter AIDS Cohort Study. Neurology 43: 2245–2252.PubMedGoogle Scholar
  11. Moore RK, Gallant J, Chaisson RE (1998). Proceedings of 12th World AIDS Conference, Geneva.Google Scholar
  12. Morris R (1984). Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11: 47–60.CrossRefPubMedGoogle Scholar
  13. Morris RG, Garrud P, Rawlins JN, O’Keefe J (1982). Place navigation impaired in rats with hippocampal lesions. Nature 297: 681–683.CrossRefPubMedGoogle Scholar
  14. Navia BA, Jordan BD, Price RW (1986). The AIDS dementia complex: I. Clinical features. Ann Neurol 19: 517–524.CrossRefPubMedGoogle Scholar
  15. Persidsky Y, Limoges J, McComb R, Bock P, Baldwin T, Tyor W, Patil A, Nottet HS, Epstein L, Gelbard H, Flanagan E, Reinhard J, Pirruccello SJ, Gendelman HE (1996). Humanimmunodeficiency virus encephalitis in SCID mice. Am J Pathol 149: 1027–1053.PubMedGoogle Scholar
  16. Riedel G, Micheau J, Lam AG, Roloff E, Martin SJ, Bridge H, Hoz L, Poeschel B, McCulloch J, Morris RG (1999). Reversible neural inactivation reveals hippocampal participation in several memory processes. Nat Neurosci 2: 898–905.CrossRefPubMedGoogle Scholar
  17. Sidman RL, Angevine JB, Pierce ET (1971) Atlas of the mouse brain and spinal cord. Cambridge, MA: Harvard University Press.Google Scholar
  18. Tross S, Price RW, Navia B, Thaler HT, Gold J, Hirsch DA, Sidtis JJ (1988). Neuropsychological characterization of the AIDS dementia complex: a preliminary report. AIDS 2: 81–88.CrossRefPubMedGoogle Scholar
  19. Tyor WR, Power C, Gendelman HE, Markham RB (1993). A model of human immunodeficiency virus encephalitis in scid mice. Proc Natl Acad Sci U S A 90: 8658–8662.CrossRefPubMedGoogle Scholar
  20. Zink WE, Anderson E, Boyle J, Hock L, Rodriguez-Sierra J, Xiong H, Gendelman HE, Persidsky Y (2002). Impaired spatial cognition and synaptic potentiation in a murine model of human immunodeficiency virus type 1 encephalitis. J Neurosci 22: 2096–2105.PubMedGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2004

Authors and Affiliations

  • William C. Griffin
    • 1
  • Lawrence D. Middaugh
    • 2
    • 3
  • Jennifer E. Cook
    • 4
  • William R. Tyor
    • 4
    • 5
    • 6
  1. 1.Center for Drug and Alcohol ProgramsMedical University of South CarolinaCharlestonUSA
  2. 2.Department of Psychiatry and Behavioral ScienceMedical University of South CarolinaCharlestonUSA
  3. 3.Department of Physiology and NeuroscienceMedical University of South CarolinaCharlestonUSA
  4. 4.Department of Microbiology and ImmunologyMedical University of South CarolinaCharlestonUSA
  5. 5.Department of NeurologyMedical University of South CarolinaCharlestonUSA
  6. 6.Neurology ServiceRalph H. Johnson VAMCCharlestonUSA

Personalised recommendations