title: HIV-1 proteins accelerate HPA axis habituation in female rats.
abstract: Congenital infection by the Human Immunodeficiency Virus (HIV) has been shown to lead to multiple co-morbidities, and people living with HIV have a higher incidence of affective and anxiety disorders. A marked increase in mood disorders is evident during the sensitive phase of adolescence and this is further pronounced in females. Depression has been linked to dysfunction of the intracellular response system to corticosteroids at the level of the hippocampus (HC) and prefrontal cortex (PFC) with a notable role of the glucocorticoid receptor (GR) and its co-chaperones (FKBP5 and FKBP4). The current study examined the extent to which HIV protein expression in adolescent female rats altered the stress response at both the level of corticosterone output and molecular regulation of the glucocorticoid receptor in the brain. WT and HIV-1 genotype female rats were randomly allocated in control, acute stress and repeat stress groups. Corticosterone plasma levels and expression of GR, FKBP4, and FKBP5 in the HC and PFC were measured. The presence of HIV-1 proteins facilitates habituation of the corticosterone response to repeated stressors, such that HIV-1 TG rats habituated to repeated restraint and WT rats did not. This was reflected by interactions between stress exposure and HIV-1 protein expression at the level of GR co-chaperones. Although expression of the GR was similarly reduced after acute and repeat stress in both genotypes, expression of FKBP5 and FKBP4 was altered in a brain-region specific manner depending on the duration of the stress exposure and the presence or absence of HIV-1 proteins. Collectively, the data presented demonstrate that HIV-1 proteins accelerate habituation to repeated stressors and modify the influence of acute and repeat stressors on GR co-chaperones in a brain region-specific manner.
authors: Department of Pediatrics, Division of Pediatric Endocrinology, Emory University, United States.
authors: Leonidas
authors: L
authors: Panagiotakopoulos
authors: Department of Physiology, Emory University, United States.
authors: Sean
authors: S
authors: Kelly
authors: Department of Physiology, Emory University, United States; Department of Psychiatry & Behavioral Sciences, Emory University, United States. Electronic address: gmccand@emory.edu.
authors: Gretchen N
authors: GN
authors: Neigh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003345:Corticosterone / Q000097:blood; D005260:Female; D006185:Habituation, Psychophysiologic / Q000502:physiology*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D008822:Mice, Transgenic; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D012149:Restraint, Physical; D012191:Retroviridae Proteins / Q000235:genetics / Q000378:metabolism*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
chemical_list: D003345:Corticosterone; D011965:Receptors, Glucocorticoid; D012191:Retroviridae Proteins; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C403485:tacrolimus binding protein 4
keywords: FKBP4; FKBP5; Female; HIV; Hippocampus; Prefrontal cortex; Stress