Abstract

Adolescents living with human immunodeficiency virus (HIV) comprise approximately 12% of the HIV-positive population worldwide. HIV-positive adolescents experience a higher rate of clinical depression, a greater risk of sexual and drug abuse behaviors, and a decreased adherence to highly active antiretroviral therapies (HAART). Using adolescent HIV-1 transgenic rats (HIV-1 tg) that display related immune response alterations and pathologies, this study tested the hypothesis that developmental expression of HIV-1-related proteins induces a depressive-like phenotype that parallels a decrease in hippocampal cell proliferation and an increase in pro-inflammatory cytokine expression in the hippocampus. Consistent with this hypothesis, adolescent HIV-1 tg rats demonstrated a depressive-like behavioral phenotype, had decreased levels of cell proliferation, and exhibited elevated expression of monocyte chemotactic protein-1 (Mcp-1) in the hippocampus relative to controls. Subsequently, we tested the ability of meloxicam, a selective COX-2 inhibitor, to attenuate behavioral deficits via inflammatory mechanisms. Daily meloxicam treatments did not alter the behavioral profile despite effectively reducing hippocampal inflammatory gene expression. Together, these data support a biological basis for the co-morbid manifestation of depression in HIV-positive patients as early as in adolescence and suggest that modifications in behavior manifest independent of inflammatory activity in the hippocampus.

Highlights

  • Successful highly active anti-retroviral therapy (HAART) has led to the unexpected consequence of aviremic complications of human immunodeficiency virus (HIV)

  • Body mass differed between HIV-1 tg rats and WT litter-mate controls such that transgenic rats weighed less than controls (t[15] = 7.12, p,0.05); total food consumed over a twoday period did not differ between WT and HIV-1 tg rats (p.0.05; Table 1)

  • In the social interaction test, HIV-1 tg rats exhibited an increased latency to interact with a novel animal (t[13] = 2.682, p,0.05; Figure 1B)

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Summary

Introduction

Successful highly active anti-retroviral therapy (HAART) has led to the unexpected consequence of aviremic complications of human immunodeficiency virus (HIV). While the cause of the higher incidence of depression among HIV-positive adolescents is unknown, the stigma of being HIVpositive and the burden of lifelong medication have been proposed to account for the increased incidence of depression [9]. Despite this relationship, similar associations between external stimuli and depression have been proposed and refuted in cases of late-life depression and post-stroke depression, implicating primary changes in neuronal function [10]. One approach that allows us to disassociate the psychosocial influences of HIV infection and the environment from the biological influences of HIV is the use of model animals

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