Evidence that the HIV-1 coat protein gp120 causes neuronal apoptosis in the neocortex of rat via a mechanism involving CXCR4 chemokine receptor

The HIV-1 coat protein, gp120 (100 ng given intracerebroventricularly (i.c. v.) daily for seven consecutive days) causes DNA fragmentation in the brain neocortex of rat. In neocortical cells bearing ultrastructural features ty pical of apoptosis, electron microscopy revealed specific immunopositivity for neurofilament cytoskeletal proteins, suggesting the neuronal nature of dying cells. Neuronal apoptosis by gp120 implicates CXCR4 chemokine recepto rs; in fact, in rats receiving a single daily, non-neurotoxic, dose of SDF- 1 alpha (0.25 pmoles given i.c.v. for 7 days before gp120), the natural lig and of CXCR4 receptor, apoptosis was significantly hindered. The mechanism of SDF-1 alpha protection involves inhibition of gp120-enhanced expression of IL-1 beta, a cytokine implicated in the mechanisms of apoptosis induced by the viral protein in the neocortex of rat. (C) 2001 Elsevier Science Ire land Ltd. All rights reserved.