NEURONAL APOPTOSIS IN HIV-INFECTION

Apart from the unique changes characteristic of <<HIV encephalitis>>, the productive infection of central nervous system by HIV, which invol ves predominantly the white matter and basal ganglia, evidence is accu mulating that the cerebral cortex may also be affected in AIDS patient s. Neuronal loss, suspected at microscopical examination, has been dem onstrated by a number of morphometric studies. However, the cause and mechanism of neuronal damage in HIV infection, are still unclear. In a n attempt to look for an apoptotic process at the origin of neuronal l oss in AIDS, we examined samples of frontal cortex, temporal cortex an d basal ganglia from 12 patients who died from AIDS and 4 HIV-positive asymptomatic cases using in situ end labelling to demonstrate charact eristic DNA fragmentation. These were compared with 5 seronegative asy mptomatic controls, and 2 seronegative patients with Alzheimer's disea se. We demonstrated neuronal apoptosis in all the AIDS cases and in th e Alzheimer's cases. Positive in situ end labelling was usually associ ated with morphological changes suggestive of neuronal apoptosis. Semi quantitative appreciation of the density of apoptotic neurons showed t hat neuronal apoptosis was more severe in atrophic brains. In contrast , no correlation was found between the density of apoptotic neurons an d the presence of HIVencephalitis or a history of cognitive disorder. Only occasional apoptotic neurons were found in one asymptomatic, HIV- positive case. Apoptosis was never observed in asymptomatic seronegati ve cases. Experimental studies tend to support our in vivo findings. I nfection by HIV of primary cultures of human embryonic central nervous system induced frequent apoptosis of neurons. No apoptotic cell was i dentified in non infected control cultures.