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

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.