title: Meloxicam blocks neuroinflammation, but not depressive-like behaviors, in HIV-1 transgenic female rats.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, United States of America; Department of Physiology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Nemeth
authors.affiliation: Department of Psychology, University of Maryland, College Park, Maryland, United States of America.
authors.forename: Erica R
authors.initials: ER
authors.lastname: Glasper
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, United States of America; Department of Physiology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Constance S
authors.initials: CS
authors.lastname: Harrell
authors.affiliation: Department of Physiology, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Sanjana A
authors.initials: SA
authors.lastname: Malviya
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Otis
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, United States of America; Department of Physiology, Emory University, Atlanta, Georgia, United States of America; Center for Behavioral Neuroscience, Emory University, Atlanta, Georgia, United States of America.
authors.forename: Gretchen N
authors.initials: GN
authors.lastname: Neigh
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003863:Depression; D005260:Female; D015870:Gene Expression; D015658:HIV Infections; D015497:HIV-1 / Q000235:genetics*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D000077239:Meloxicam; D051381:Rats; D055647:Rats, Transgenic; D013843:Thiazines / Q000008:administration & dosage / Q000494:pharmacology*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018932:Chemokine CCL2; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam