HIV-1 Envelope Glycoprotein 120 Induced Neuroinflammation Does Not Result in Neurocognitive Impairment in an in vivo Rat Model

Human immunodeficiency virus-1 (HIV-1) infected patients are increasingly experiencing neurocognitive deficits due to low level viral replication and associated inflammation in the central nervous system which results in cellular apoptosis in the brain. The aim of this MSc project was to examine cognitive impairments in learning/memory in the Morris Water Maze using our recently implemented in vivo rat model of HIV-1-induced neuroinflammation by intracerebroventricular administration of HIV-1 gp120ADA. Our findings illustrate that a single dose of 8μg R5-tropic HIV-1 gp120ADA or 50μg lipopolysaccharide elicited a robust proinflammatory cytokine (IL-1β, TNFα) and oxidative stress (iNOS) response in the brain, but only lipopolysaccharide administration activated caspase-3 expression in hippocampal neurons, possibly, resulting in the observed spatial learning/memory deficits. Our gp120ADA-induced neuroinflammatory rat model suggests that acute administration of HIV-1 viral coat protein does not result in neurocognitive impairments, thus alternative gp120 dosing regimens should be considered to establish a model of neurocognitive deficits.M.Sc