Date of Award
1-1-2022
Document Type
Thesis
Degree Name
M.S. in Pharmaceutical Science
First Advisor
Dr. John Rimoldi
Second Advisor
Dr. Jason Paris
Third Advisor
Dr. Nicole Ashpole
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Human immunodeficiency virus (HIV) persists as a global pandemic. Despite the benefits of combinatorial antiretroviral therapies (cART), virotoxic HIV proteins are still detectable within the central nervous system and approximately half of all cART-treated patients contend with neurological impairments. The mechanisms underlying these effects are not known, but likely involve actions of virotoxic HIV proteins including glycoprotein 120 (gp120). Glycoprotein 120 is neurotoxic, in part due to its capacity to activate microglia. Corticosterone, an endogenous anti-inflammatory, has been found to attenuate neuronal death caused by gp120-induced microglial cytokine production in vitro. But, the concentration-dependent effects of corticosterone to influence microglial activation state and the associated behavioral outcomes are not known. Herein, we conducted parallel in vitro and in vivo studies using a microglial cell line and transgenic mice that constitutively-expressed gp120. We assessed gp120 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, but only at an optimal concentration (100 nM) and not at resting (32 nM) or high physiological (320 nM) concentrations. Transgenic mice expressing gp120 demonstrated greater anxiety-like behavior on an elevated plus maze and greater gp120-exposure was associated with motor deficits and anxiety-like behavior in an open field; albeit, anxiety-like behavior was lower in a light-dark transition test. Circulating corticosterone was lower in gp120-expressing males and diestrous (but not proestrous) females compared to their respective wildtype counterparts. Greater circulating corticosterone was associated with reduced anxiety-like behavior whereas a greater duration of exposure to gp120 was associated with increased anxiety-like behavior. These associations were not observed among wildtype mice. These findings may demonstrate a capacity for glucocorticoids to attenuate gp120-mediated neuroinflammation and anxiety-like behavior.
Recommended Citation
Moss, Emaya Marie, "Physiological Corticosterone Attenautes GP120-Mediated Microglial Activation and is Associated with Reduced Anxiety-Like Behavior in GP120-Expressing Mice" (2022). Electronic Theses and Dissertations. 2449.
https://egrove.olemiss.edu/etd/2449
Concentration/Emphasis
Pharmacology