Human immunodeficiency virus-1 coat protein gp120 impairs contextual fear conditioning: a potential role in AIDS related learning and memory impairments

Many AIDS patients suffer from cognitive impairments including deficits in learning and memory, The Human Immunodeficiency Virus-1 (HIV-1) envelope gl ycoprotein gp120 is one possible mediator of these impairments, This is bec ause gp120 activates brain microglial cells and astrocytes, and in vivo act ivation of glia leads to the release of the proinflammatory cytokine interl eukin-l beta (IL-1 beta). gp120 induced IL-1 beta release could be involved in producing memory impairments associated with AIDS because central IL-1 beta activity adversely affects cognitive function. The reported experiment s evaluated the effects of i.c.v. gp120 administration and subsequent IL-1 beta activity on learning and memory processes in the rat, Intracerebrovent ricular gp120 produced memory impairments on hippocampally dependent contex tual fear conditioning, but not hippocampally independent auditory-cue fear conditioning following post-conditioning gp120 administration. Central gp1 20 administration also caused increases in IL-1 beta protein levels in the hippocampus and frontal cortex but not in the hypothalamus. gp120 induced m emory impairments were blocked by 2, different IL-I antagonists, alpha mela nocyte stimulating hormone (alpha MSH) and interleukin-l receptor antagonis t (IL-1ra). Finally, heat denaturation of the tertiary structure of gp120 a bolished its effects on fear conditioning, suggesting that gp120 impairs co ntextual feat conditioning by binding to its receptors on glia. (C) 2000 Pu blished by Elsevier Science B.V. All rights reserved.