A NEURONAL AND NEUROANATOMICAL CORRELATE OF HIV-1 ENCEPHALOPATHY RELATIVE TO HIV-1 ENCEPHALITIS IN HIV-1-INFECTED CHILDREN

Progressive central nervous system dysfunction analogous to the AIDS d ementia complex (ADC) seen in adults (HIV-1-associated progressive enc ephalopathy or HIV-1 encephalopathy) commonly occurs in HIV-1-infected children. The cause appears to be directly or indirectly related to H IV-1, rather than to other opportunistic pathogens. The exact mechanis m(s) by which the virus affects brain function is not known. To determ ine whether the virus might modify brain function via an alteration in cortical neurons, we examined peptide neurotransmitter expression in the frontal cortex of HIV-1-infected cases with clinical HIV-1 encepha lopathy relative to pathologic HIV-1 encephalitis. In situ hybridizati on was used to determine the level of peptide neurotransmitter express ion of somatostatin in the frontal cortex of cases with and without HI V-1 encephalopathy and/or HIV-1 encephalitis. A 2-fold higher number o f preprosomatostatin mRNA-positive interneurons was present in layer I V of cases with HIV-1 encephalitis compared with cases without HIV-1 e ncephalitis. In cases with PE, this neuronal alteration was 4- to 5-fo ld higher than in cases without PE, and was present in subcortical whi te matter in addition to layer IV. In cases having both PE and HIV-1 e ncephalitis, and in cases with HIV-1 encephalitis alone, these neurona l alterations in layer TV and/or subcortical white matter related to d isseminated microglial nodules, even when these potentially viral-infe cted cells were negative for HIV-1 p24 antigen, a marker of productive viral infection. An alteration in preprosomatostatin mRNA-expressing cells occurring with HIV-1 encephalitis may be at least one mechanism that contributes to HIV-1 encephalopathy. When compared with other cor tical laminae, layer IV receives most of its synaptic input from the m ediodorsal nucleus of the thalamus. Neurons in the subcortical white m atter project to the thalamus. The thalamus has been shown to have hig h amounts of viral antigen and increased metabolic activity in patient s with AIDS. An alteration in preprosomatostatin mRNA-expressing cells may play a role in HIV-1 encephalopathy.