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 glycoprotein gp120 is one possible mediator of these impairments. This is because gp120 activates brain microglial cells and astrocytes, and in vivo activation of glia leads to the release of the proinflammatory cytokine interleukin-1 beta (IL-1beta). gp120 induced IL-1beta release could be involved in producing memory impairments associated with AIDS because central IL-1beta activity adversely affects cognitive function. The reported experiments evaluated the effects of i.c.v. gp120 administration and subsequent IL-1beta activity on learning and memory processes in the rat. Intracerebroventricular gp120 produced memory impairments on hippocampally dependent contextual fear conditioning, but not hippocampally independent auditory-cue fear conditioning following post-conditioning gp120 administration. Central gp120 administration also caused increases in IL-1beta protein levels in the hippocampus and frontal cortex but not in the hypothalamus. gp120 induced memory impairments were blocked by 2 different IL-1 antagonists, alpha melanocyte stimulating hormone (alphaMSH) and interleukin-1 receptor antagonist (IL-1ra). Finally, heat denaturation of the tertiary structure of gp120 abolished its effects on fear conditioning, suggesting that gp120 impairs contextual fear conditioning by binding to its receptors on glia.
Pugh
C R
CR
Department of Psychology, University of Colorado, Boulder, CO 80309, USA. rachal@psych.colorado.edu
Johnson
J D
JD
Martin
D
D
Rudy
J W
JW
Maier
S F
SF
Watkins
L R
LR
D015526:AIDS Dementia Complex / Q000378:metabolism* / Q000523:psychology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D003463:Cues; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D015699:HIV Envelope Protein gp120; D007375:Interleukin-1