Meloxicam Blocks Neuroinflammation, but Not Depressive-Like Behaviors, in HIV-1 Transgenic Female Rats

• Type of Material: Article
• Authors: Christina L. Nemeth, Emory University; Erica R. Glasper, University of Maryland; Constance S. Harrell, Emory University; Sanjana A. Malviya, Emory University; Jeffrey Otis, Emory University; Gretchen Neigh, Emory University
• Language: English
• Date: 2014-10-01
• Publisher: Public Library of Science
• Publication Version: Final Published Version
• Copyright Statement: © 2014 Nemeth et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.pone.0108399
• Title of Journal or Parent Work: PLoS ONE
• ISSN: 1932-6203
• Volume: 9
• Issue: 10
• Start Page: e108399
• End Page: e108399
• Grant/Funding Information: The authors would like to acknowledge the financial support of The Department of Physiology, Emory University, Atlanta, GA. Additionally, this research was supported by the Creative and Novel Ideas in HIV Research Program (CNIHR) through a supplement to the University of Alabama at Birmingham (UAB) Center For AIDS Research funding (P30 AI027767-24).; This funding was made possible by collaborative efforts of the Office of AIDS Research, the National Institutes of Allergies and Infectious Diseases, and the International AIDS Society. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: Science & Technology - Other Topics; DYSFUNCTION; Science & Technology; ADHERENCE; BRAIN; HIPPOCAMPAL NEUROGENESIS; AIDS; MODEL; CYTOKINES; SYMPTOMS; ANTIDEPRESSANT TREATMENT; MAJOR DEPRESSION; Multidisciplinary Sciences
• Research Categories: Health Sciences, General; Psychology, Physiological; Biology, Neuroscience

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.