Sas Andrew R, Bimonte-Nelson Heather A, Tyor William R
Medical University of South Carolina, Department of Microbiology and Immunology, USA.
AIDS. 2007 Oct 18;21(16):2151-9. doi: 10.1097/QAD.0b013e3282f08c2f.
Interferon alpha (IFNalpha) is an antiviral cytokine produced in response to viral infection. IFNalpha also acts as a neuromodulatory molecule in the central nervous system (CNS). Elevated IFNalpha in the CNS causes cognitive deficits.
To determine if elevated levels of IFNalpha in an HIV encephalitis mouse model correlate with cognitive deficits.
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 IFNalpha expression.
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 IFNalpha 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, IFNalpha levels in the brain correlated directly with working memory errors for mice with HIV infected macrophages.
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 IFNalpha.
干扰素α（IFNα）是一种在病毒感染时产生的抗病毒细胞因子。IFNα在中枢神经系统（CNS）中也作为一种神经调节分子发挥作用。中枢神经系统中IFNα水平升高会导致认知缺陷。
确定HIV脑炎小鼠模型中IFNα水平升高是否与认知缺陷相关。
将HIV感染或未感染（对照）的巨噬细胞脑内接种（i.c.）到C57BL/6J SCID小鼠中，并在水迷宫逃避实验中对其进行认知测试。行为测试完成后，采用免疫组织化学和酶联免疫吸附测定（ELISA）检测脑病理学和IFNα表达。
脑内注射HIV感染巨噬细胞的小鼠表现出明显更多的工作记忆错误，尤其是在记忆负荷最高的实验中。免疫组织化学显示，与注射未感染对照巨噬细胞的小鼠相比，注射HIV感染巨噬细胞的小鼠脑内神经元和神经胶质细胞上小鼠IFNα染色增加。此外，对于注射HIV感染巨噬细胞的小鼠，脑内IFNα水平与工作记忆错误直接相关。
这些数据表明，C57BL/6J SCID小鼠感染HIV感染巨噬细胞后出现的认知缺陷是由感染诱导的IFNα增加介导的。
