Physiological Corticosterone Attenuates gp120-Mediated Microglial Activation and Is Associated with Reduced Anxiety-Like Behavior in gp120-Expressing Mice

Abstract

Despite the benefits of combinatorial antiretroviral therapies (cART), virotoxic HIV proteins are still detectable within the central nervous system. Approximately half of all cART-treated patients contend with neurological impairments. The mechanisms underlying these effects likely involve virotoxic HIV proteins, including glycoprotein 120 (gp120). Glycoprotein-120 is neurotoxic due to its capacity to activate microglia. Corticosterone has been found to attenuate neuronal death caused by gp120-induced microglial cytokine production in vitro. However, the concentration-dependent effects of corticosterone on microglial activation states and the associated behavioral outcomes are unclear. Herein, we conducted parallel in vitro and in vivo studies to assess gp120-mediated effects on microglial activation, motor function, anxiety- and depression-like behavior, and corticosterone’s capacity to attenuate these effects. We found that gp120 activated microglia in vitro, and corticosterone attenuated this effect at an optimal concentration of 100 nM. Transgenic mice expressing gp120 demonstrated greater anxiety-like behavior on an elevated plus maze, and a greater duration of gp120 exposure was associated with motor deficits and anxiety-like behavior. Circulating corticosterone was lower in gp120-expressing males and diestrous females. Greater circulating corticosterone was associated with reduced anxiety-like behavior. These findings may demonstrate a capacity for glucocorticoids to attenuate gp120-mediated neuroinflammation and anxiety-like behavior.

Deciphering the Association of Epstein–Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice

“…Similarly, the time spent in the arms as well as the time taken to travel increased in G3 and G4 ( p < 0.01) (Figure III,IV). Earlier, transgenic mice expressing human immunodeficiency virus glycoprotein 120 (HIV-gp120) indicated anxiety-like behavior on an elevated-plus maze, and chronic exposure to gp120 was found to be associated with motor deficits . These anxiety/depression-like behaviors and locomotor activity impairment were observed in mice infected with USA300 Staphylococcus aureus compared to the control.…”