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NFkappaB activation, TNF-alpha expression, and apoptosis in the AIDS-Dementia-Complex
K Rostasy1, L Monti, C Yiannoutsos
1Department of Psychiatry, New England Medical Center, Boston, MA 02111, USA.
Journal of Neurovirology
|February 15, 2001
Summary
Nuclear factor kappa B (NFkappaB) activation in HIV-infected brains correlates with inflammation and cell death, particularly in the basal ganglia, linking it to cognitive decline in ADC patients.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- The role of NFkappaB activation, inflammatory mediators, and apoptosis in the HIV-infected brain remains unclear.
- Understanding these factors is crucial for addressing HIV-associated neurocognitive disorders (HAND).
Purpose of the Study:
- To investigate the cellular and regional distribution of NFkappaB, TNF-alpha, and apoptosis in the HIV-infected brain.
- To determine the relationship between these factors and the severity of HIV-associated dementia (ADC).
Main Methods:
- Examined frontal cortex (FC), deep white matter (DWM), and basal ganglia (BG) in 17 ADC patients.
- Utilized nuclear staining for NFkappaB, and TUNEL staining for apoptosis.
- Assessed expression of HLA-DR, iNOS, TNF-alpha, and gp41.
Main Results:
- NFkappaB localized to microglia/macrophages in BG and DWM, correlating with ADC severity.
- Correlations found between NFkappaB, HLA-DR, iNOS, TNF-alpha, gp41, and apoptosis.
- Increased TUNEL-positive cells in BG correlated with ADC stage and cognitive impairment.
Conclusions:
- NFkappaB activation is linked to inflammatory mediators and apoptosis in the HIV-infected brain.
- These processes, particularly in the basal ganglia, are associated with ADC severity and cognitive decline.