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

• Published in: Viruses 2023-02, Vol.15 (2), p.424
• Main Authors: Moss, Emaya M, Mahdi, Fakhri, Worth, Charlie J, Paris, Jason J
• Format: Article
• Language: English
• Subjects: affective behavior; Age; Animals; Anxiety; Behavior; Care and treatment; Central nervous system; Central nervous system diseases; Complications and side effects; Corticosterone; Female; Females; Glucocorticoids; glycoprotein 120; Glycoprotein gp120; Glycoproteins; Health aspects; HIV; HIV infection; Human immunodeficiency virus; Inflammation; Laboratory animals; Male; Mice; Mice, Transgenic; Microglia; Morphology; Neurotoxicity; Physiology; Proteins; Risk factors; Testing; Transgenic animals; Transgenic mice
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v15020424

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 . 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.