Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis

Apoptosis of neurones, macrophages, and microglia occurs in the brains of p aediatric patients with human immunodeficiency virus (HIV) type 1 encephali tis, which is often associated with pre-mortem neurological disease (progre ssive encephalopathy). We have previously reported that TUNEL-positive neur ones in brain tissue from paediatric patients with HIV type 1 encephalitis and progressive encephalopathy are strikingly devoid of the pro-apoptotic g ene product Bar, in marked contrast to brain-resident macrophages and micro glia. Using immunocytochemical methods, the present study demonstrate that neurones in patients with HIV type 1 encephalitis and progressive encephalo pathy, as well as macrophages and microglia, but not astrocytes, overexpres s caspase-3, a pro-apoptotic enzyme that is proteolytically activated downs tream of Bax-Bcl-2 dysregulation. Go-localization of neuronal cytoplasmic c aspase-3 and nuclear TUNEL, staining, a marker for fragmented DNA, was also infrequently observed in brain tissue from patients with HIV type 1 enceph alitis and progressive encephalopathy. These findings suggest that vulnerab le neurones in brain tissue from patients with HIV virus type 1 encephaliti s and progressive encephalopathy undergo apoptosis by a mechanism that invo lves upregulation of caspase-3 in a pathway that is independent of Bax-Bcl- 2 dysregulation. Furthermore, caspase-1 upregulation in apoptotic neurones likely occurs prior to DNA fragmentation.