Cognitive dysfunction in HIV encephalitic SCID mice correlates with levels of Interferon-α in the brain

Andrew R. Sas, Heather Bimonte-Nelson, William R. Tyor

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

BACKGROUND: Interferon alpha (IFNα) is an antiviral cytokine produced in response to viral infection. IFNα also acts as a neuromodulatory molecule in the central nervous system (CNS). Elevated IFNα in the CNS causes cognitive deficits. OBJECTIVE: To determine if elevated levels of IFNα in an HIV encephalitis mouse model correlate with cognitive deficits. METHODS: C57BL/6J SCID mice were inoculated intracerebrally (i.c.) with HIV infected or uninfected (control) macrophages and cognitively tested in a water escape radial arm maze. After behavioral testing was completed, immunohistochemistry and ELISA were used to examine brain pathology and IFNα expression. RESULTS: Mice injected i.c. with HIV infected macrophages exhibited significantly more working memory errors, particularly in trials with the highest memory load. Immunohistochemistry indicated increased mouse IFNα staining prevalent on neurons and glial cells in the brains of mice with HIV infected macrophages compared to mice with uninfected control macrophages. In addition, IFNα levels in the brain correlated directly with working memory errors for mice with HIV infected macrophages. CONCLUSIONS: These data suggest that the cognitive deficit noted for the C57BL/6J SCID mice with HIV infected macrophages is mediated by the infection induced increase in IFNα.

Original languageEnglish (US)
Pages (from-to)2151-2159
Number of pages9
JournalAIDS
Volume21
Issue number16
DOIs
Publication statusPublished - Oct 2007

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Keywords

  • Animal model
  • Cytokines
  • HIV
  • Neurological
  • Viral infections

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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