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Bourke C.H.,Emory University | Neigh G.N.,Emory University | Neigh G.N.,Center for Behavioral Neuroscience | Neigh G.N.,Comprehensive NeuroScience
Hormones and Behavior | Year: 2011

Evidence suggests that women are more susceptible to stress-related disorders than men. Animal studies demonstrate a similar female sensitivity to stress and have been used to examine the underlying neurobiology of sex-specific effects of stress. Although our understanding of the sex-specific effects of chronic adolescent stress has grown in recent years, few studies have reported the effects of adolescent stress on depressive-like behavior. The purpose of this study was to determine if a chronic mixed modality stressor (consisting of isolation, restraint, and social defeat) during adolescence (PND 37-49) resulted in differential and sustained changes in depressive-like behavior in male and female Wistar rats. Female rats exposed to chronic adolescent stress displayed decreased sucrose consumption, hyperactivity in the elevated plus maze, decreased activity in the forced swim test, and a blunted corticosterone response to an acute forced swim stress compared to controls during both adolescence (PND 48-57) and adulthood (PND 96-104). Male rats exposed to chronic adolescent stress did not manifest significant behavioral changes at either the end of adolescence or in adulthood. These data support the proposition that adolescence may be a stress sensitive period for females and exposure to stress during adolescence results in behavioral effects that persist in females. Studies investigating the sex-specific effects of chronic adolescent stress may lead to a better understanding of the sexually dimorphic incidence of depressive and anxiety disorders in humans and ultimately improve prevention and treatment strategies. © 2011 .

Bourke C.H.,Emory University | Neigh G.N.,Emory University | Neigh G.N.,Center for Behavioral Neuroscience | Neigh G.N.,Comprehensive NeuroScience
Behavioural Brain Research | Year: 2012

The stress response is a multifaceted physiological reaction that engages a wide range of systems. Animal studies examining stress and the stress response employ diverse methods as stressors. While many of these stressors are capable of inducing a stress response in animals, a need exists for an ethologically relevant stressor for female rats. The purpose of the current study was to use an ethologically relevant social stressor to induce behavioral alterations in adult female rats. Adult (postnatal day 90) female Wistar rats were repeatedly exposed to lactating Long Evans female rats to simulate chronic stress. After six days of sessions, intruder females exposed to defeat were tested in the sucrose consumption test, the forced swim test, acoustic startle test, elevated plus maze, and open field test. At the conclusion of behavioral testing, animals were restrained for 30. min and trunk blood was collected for assessment of serum hormones. Female rats exposed to maternal aggression exhibited decreased sucrose consumption, and impaired coping behavior in the forced swim test. Additionally, female rats exposed to repeated maternal aggression exhibited an increased acoustic startle response. No changes were observed in female rats in the elevated plus maze or open field test. Serum hormones were unaltered due to repeated exposure to maternal aggression. These data indicate the importance of the social experience in the development of stress-related behaviors: an acerbic social experience in female rats precipitates the manifestation of depressive-like behaviors and an enhanced startle response. © 2011 Elsevier B.V.

Bourke C.H.,Emory University | Harrell C.S.,Emory University | Neigh G.N.,Emory University | Neigh G.N.,Center for Behavioral Neuroscience | Neigh G.N.,Comprehensive NeuroScience
Hormones and Behavior | Year: 2012

This article is part of a Special Issue "Neuroendocrine-Immune Axis in Health and Disease.". Clinical evidence has indicated that women are more susceptible to stress-related and autoimmune disorders than men. Although females may be more susceptible to some disease states, males do not escape unscathed and are more susceptible to metabolic dysfunction. The hypothalamic-pituitary-axis plays a pivotal role in the sexually dimorphic effects of chronic stress through alterations in negative feedback. Recent evidence has implicated the glucocorticoid receptor and its co-chaperones in the etiology of psychiatric and somatic diseases. Gonadal hormones heavily interact with both glucocorticoid receptor expression and glucocorticoid receptor action either through direct or indirect effects on proteins in the chaperone and co-chaperone complex. Diverse systems including the hypothalamic-pituitary-axis, the immune system, and metabolism are affected differently in males and females, possibly through the glucocorticoid receptor system. New considerations of glucocorticoid regulation through the co-chaperone complex in the brain will be vital to the development of treatment strategies for men and women afflicted by neuropsychiatric and somatic disorders. © 2012 Elsevier Inc.

Meyer K.,Leibniz Institute for Neurobiology | Meyer K.,Otto Von Guericke University of Magdeburg | Korz V.,Otto Von Guericke University of Magdeburg | Korz V.,Center for Behavioral Neuroscience
Hormones and Behavior | Year: 2013

Estrogen and estrogenic functions are age-dependently involved in the modulation of learning, memory and mood in female humans and animals. However, the investigation of estrogenic effects in males has been largely neglected. Therefore, we investigated the hippocampal gene expression of estrogen receptors α and β (ERα, β) in 8-week-old, 12-week-old and 24-week-old male rats. To control for possible interactions between the expression of the estrogen receptor genes and other learning-related steroid receptors, androgen receptors (AR), corticosterone-binding glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) were also measured. Furthermore, the concentrations of the ligands 17β-estradiol, testosterone and corticosterone were measured. The spatial training was conducted in a hole-board. The 8-week-old rats exhibited higher levels of general activity and exploration during the training and performed best with respect to spatial learning and memory, whereas no difference was found between the 12-week-old and 24-week-old rats. The trained 8-week-old rats exhibited increased gene expression of ERα compared with the untrained rats in this age group as well as the trained 12-week-old and 24-week-old rats. The concentrations of estradiol and testosterone, however, were generally higher in the 24-week-old rats than in the 8-week-old and 12-week-old rats. The ERα mRNA concentrations correlated positively with behavior that indicate general learning motivation. These results suggest a specific role of ERα in the age-related differences in motivation and subsequent success in the task. Thus, estrogen and estrogenic functions may play a more prominent role in young male behavior and development than has been previously assumed. © 2012 Elsevier Inc.

Bourke C.H.,Emory University | Raees M.Q.,Emory University | Malviya S.,Emory University | Bradburn C.A.,Emory University | And 5 more authors.
Psychoneuroendocrinology | Year: 2013

Early life stress precipitates dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and this effect is most pronounced in females. The mechanisms that mediate female sensitivity to stress-induced HPA axis dysregulation are unknown. The purpose of this study was to determine whether sex moderates the effects of chronic adolescent stress on glucocorticoid receptor (GR) translocation and moderators of the GR system. Female adolescent rats with a history of chronic stress exposure demonstrated a delayed resolution of the plasma corticosterone response to an acute stressor and this delay was accompanied by attenuated GR translocation compared to control adolescent females. The chronic stress-induced phenotype in females was similar to the baseline phenotype in male adolescent rats. Conversely, the expression patterns of GR moderators/co-chaperones became more sexually dimorphic following chronic stress, suggesting divergent function of the GR system between male and female adolescent rats. Gene expression of Ppid, a positive regulator of the GR, was predicted by plasma estradiol and 34% lower in control adolescent females than males, indicating that sex steroids may play a role in the sexually dimorphic response. After chronic adolescent stress, females displayed elevated hippocampal expression of Bag1 and Ppid genes that was not observed in males. Overall, the GR output to an acute stressor, illustrated by transcription of Nr3c1 (encoding the GR), Bag1, Fkbp5, Ppid, and Src1, was significantly upregulated and differed in a sex-specific and chronic stress-dependent manner. This study provides new evidence for sex differences during development and adaptation of the glucocorticoid receptor chaperone system. © 2012 Elsevier Ltd.

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