The Effects of HIV-1 GP120 on the Puncta Count and Expression of α5-Containing GABAA Receptors in Cultured Rat Hippocampal Neurons

[Speaker] Adrienne Y Jo:1
[Co-author] Matthew Green:2, Stanley A Thayer:2
1:Claremont McKenna College, USA, 2:University of Minnesota, USA

Approximately 50% of the >30 million people worldwide affected by human immunodeficiency virus-1 (HIV-1) suffer from cognitive impairments known as HIV-1-associated neurocognitive disorders (HAND). HIV-1 can infect microglia, leading to the release of toxic proteins, such as envelope glycoprotein 120 (gp120IIIB), which causes neurotoxicity and synaptodendritic damage. Gp120 is known to induce the release of interleukin-1β (IL-1β), a cytokine released by microglia. Previous work shows that IL-1β increases the function of α5-containing GABAA receptors (α5-GABAA-Rs), which lowers cell excitability and may contribute to cognitive impairments. Thus, we tested whether gp120 would increase the expression of protein clusters of α5-GABAA-Rs in primary hippocampal cultures derived from embryonic day 17 Sprague Dawley® rats. Immunocytochemistry was performed to examine the localization of α5-GABAA-Rs relative to microtubule-associated protein 2 (MAP2) immunoreactivity. Based on previous electrophysiology experiments on α5-GABAA-Rs, we hypothesize that gp120 increases α5 puncta. Preliminary data demonstrates that gp120 leads to a trending increase in α5 puncta, which might explain the increased neuronal inhibition and decreased cell excitability seen in vitro. Altered excitability may lead to the cognitive impairments found in HAND patients. Thus, inhibition of α5-GABAA-Rs may be a novel target for the treatment of HAND.

Advanced Search