Differential long-term neurotoxicity of HIV-1 proteins in the rat hippocampal formation: a design-based stereological study.

The human immunodeficiency virus type 1 (HIV-1) proteins, gp120 and Tat, are believed to play a role in mediating central nervous system (CNS) pathology in HIV-1 infected patients. Using design-based stereology, we examined the role of neonatal intrahippocampal injections of gp120 and Tat on the adult hippocampus ( approximately 7(1/2) month). Postnatal day (P)1-treated Sprague-Dawley rats were bilaterally injected with vehicle (VEH, 0.5 microl sterile buffer), gp120 (100 ng), Tat (25 microg) or combined gp120 + Tat (100 ng + 25 microg). Using Nissl-stained tissue sections, we quantified total neurons in five subregions of the rat hippocampus [granual layer (GL), hilus of the dentate gyrus (DGH), cornu ammonis fields (CA)2/3, CA1, and subiculum (SUB)], and total glial cells (astrocytes and oligodendrocytes) in two subregions (DGH and SUB). Estimates of cell area and cell volume were taken in the DGH. There was a significant reduction of neuron number in the CA2/3 subfield by Tat and gp120, and a significant reduction in the DGH by Tat only. For glial cells, numbers of astrocytes in the DGH and SUB were increased by the Tat protein, whereas no effects were noted for gp120. Finally, for oligodendrocytes Tat increased cell number in the DGH but not in any other region; gp120 had no detectable effect in any brain region. Estimates of cell area and cell volume of the three different cell types revealed no significant differences between treatments. Collectively, these results suggest differential effects of gp120 and Tat on the estimated total number of neurons, as well as on the number of glial cells. (c) 2007 Wiley-Liss, Inc.