Background: HIV dementia (HIVD) is one of the most important neurological complications associated with HIV infection. Neuroglial dysfunction and apoptosis has been hypothesized as a pathogenic mechanism in HIVD. We studied the Fas/FasL pathway and its association with astroglial and microglial reactions in HIVD.

Methods: By Western blot analysis, the expression of Fas , FasL, and GFAP was studied in 10 HIVD clinically characterized patients (pts), 7 HIV positive non-demented and 8 age-matched HIV negative controls. Three (3) areas of the brain were studied: basal ganglia (BG), mid-frontal gyrus (MFG), and deep white matter (DWM)). Values were standardized by densitometry analysis and a ratio of expression was obtained using Actin as the housekeeping protein. Tissue sections from the same group of pts were used for immunocytochemistry and laser confocal microscopy to evaluate the cellular expression of Fas, FasL, and apoptotic mediators such as caspase 3. A quantitative analysis of the magnitude of astroglial and microglial reactions was also obtained and compared with Western blot analysis.

Results: Using linear regression analysis our study demonstrated a significant upregulation in HIVD of Fas and FasL in BG ( p = 0.05 and p = 0.03), of Fas in DWM (p = 0.03) and of FasL in MFG (p = 0.01) as compared to HIV negative controls. GFAP expression was upregulated in HIVD in BG and MFG (p = 0.01, p = 0.02). Western blot results were comparable to those obtained by immunocytochemical cell counting. Confocal microscopy demonstrated the presence of FasL in astrocytes, macrophages, microglia, oligodendrocytes, and lymphocytes. Fas was expressed in infiltrating macrophages and to lesser extent in astrocytes. Caspase 3, in the activated form, was analyzed in duality with GFAP and observed in numerous astrocytes in all 3 groups studied. Caspase 3 was also observed in many macrophages.

Conclusions: Fas and FasL pathways seem to be involved in HIVD and their greater expression in macrophages may suggest roles in inflammation and apoptosis. The potential role of Fas/FasL in astrocyte dysfunction may be associated with inflammatory mechanisms rather than apoptosis.