Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.

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Changes in masculine sexual behavior, corticosterone and testosterone in response to acute and chronic stress in male rats

Hormones and Behavior ◽

10.1016/j.yhbeh.2003.04.001 ◽

2003 ◽

Vol 44 (4) ◽

pp. 327-337 ◽

Cited By ~ 117

Author(s):

S Retana-Márquez ◽

H Bonilla-Jaime ◽

G Vázquez-Palacios ◽

R Martínez-García ◽

J Velázquez-Moctezuma

Keyword(s):

Sexual Behavior ◽

Chronic Stress ◽

Male Rats ◽

Acute And Chronic Stress

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Effect of Voluntary Exercise Training on Corticosterone Level and Immobility Behavior Induced by Chronic Stress in Rats

Caspian Journal of Neurological Sciences ◽

10.32598/cjns.6.22.6 ◽

2020 ◽

Vol 6 (3) ◽

pp. 164-169

Author(s):

Zahra Entezari ◽

◽

Ayyub Babaei ◽

Saleh Rahmati-Ahmadabad ◽

◽

...

Keyword(s):

Exercise Training ◽

Chronic Stress ◽

Exercise Group ◽

Voluntary Exercise ◽

Male Rats ◽

Depression Symptoms ◽

Chronic Unpredictable Stress ◽

Corticosterone Concentration ◽

Serum Corticosterone ◽

Immobility Time

Background: Depression is a common mood disorder that in the long-term impairs thoughts, behavior, feelings, and health. Chronic unpredictable stress is one of the factors that can cause depression. Objectives: To investigate the effect of voluntary exercise training on immobility behavior (caused by chronic unpredictable stress) and serum corticosterone concentration. Materials & Methods: A total of 24 male rats were randomly and equally assigned to four groups of healthy-control, healthy-exercise, depressed-control, and depressed-exercise. Depressed-control and depressed-exercise groups were first exposed to three weeks of chronic unpredictable stress. After this period, the exercise groups performed four weeks of voluntary exercise training. Twentyfour hours after the last training session, a forced swim test was taken from the rats and their blood samples were taken 24 hours later. The obtained data were analyzed using a 2-way analysis of variance (significance level: P<0.05). The Pearson correlation coefficient was used to examine the relationship between study variables. All statistical analyses were performed in SPSS v. 22. Results: Chronic stress increased immobility behavior (P=0.001) and serum corticosterone concentration (P=0.001). In contrast, exercise training reduced immobility behavior (P=0.001) and serum corticosterone (P=0.001). The immobility time (P=0.001) and serum corticosterone concentration in the depressed-exercise group were higher than those in the healthy-exercise group (P=0.001). There was a positive correlation between immobility behavior and serum corticosterone concentration (r=0.85 and P=0.001). Conclusion: While the chronic stress increases the immobility behavior and serum corticosterone concentration, voluntary exercise training can reduce immobility behavior and serum corticosterone and adjust some depression symptoms.

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Environmental enrichment protects against the effects of chronic stress on cognitive and morphological measures of hippocampal integrity

Neurobiology of Learning and Memory ◽

10.1016/j.nlm.2012.01.003 ◽

2012 ◽

Vol 97 (2) ◽

pp. 250-260 ◽

Cited By ~ 61

Author(s):

Katie M. Hutchinson ◽

Katie J. McLaughlin ◽

Ryan L. Wright ◽

J. Bryce Ortiz ◽

Danya P. Anouti ◽

...

Keyword(s):

Chronic Stress ◽

Environmental Enrichment

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Effects of environmental enrichment on self-administration of the short-acting opioid remifentanil in male rats

Psychopharmacology ◽

10.1007/s00213-017-4734-2 ◽

2017 ◽

Vol 234 (23-24) ◽

pp. 3499-3506 ◽

Cited By ~ 7

Author(s):

Rebecca S. Hofford ◽

Jonathan J. Chow ◽

Joshua S. Beckmann ◽

Michael T. Bardo

Keyword(s):

Environmental Enrichment ◽

Male Rats ◽

Self Administration ◽

Short Acting

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Hypoactivity of the Hypothalamo-Pituitary-Adrenocortical Axis during Recovery from Chronic Variable Stress

Endocrinology ◽

10.1210/en.2005-1041 ◽

2006 ◽

Vol 147 (4) ◽

pp. 2008-2017 ◽

Cited By ~ 113

Author(s):

Michelle M. Ostrander ◽

Yvonne M. Ulrich-Lai ◽

Dennis C. Choi ◽

Neil M. Richtand ◽

James P. Herman

Keyword(s):

Mrna Expression ◽

Chronic Stress ◽

Hpa Axis ◽

Male Rats ◽

Plasma Acth ◽

Novel Environment ◽

Systemic Hypoxia ◽

Delayed Recovery ◽

Chronic Variable Stress

Chronic stress induces both functional and structural adaptations within the hypothalamo-pituitary-adrenocortical (HPA) axis, suggestive of long-term alterations in neuroendocrine reactivity to subsequent stressors. We hypothesized that prior chronic stress would produce persistent enhancement of HPA axis reactivity to novel stressors. Adult male rats were exposed to chronic variable stress (CVS) for 1 wk and allowed to recover. Plasma ACTH and corticosterone levels were measured in control or CVS rats exposed to novel psychogenic (novel environment or restraint) or systemic (hypoxia) stressors at 16 h, 4 d, 7 d, or 30 d after CVS cessation. Plasma ACTH and corticosterone responses to psychogenic stressors were attenuated at 4 d (novel environment and restraint) and 7 d (novel environment only) recovery from CVS, whereas hormonal responses to the systemic stressor were largely unaffected by CVS. CRH mRNA expression was up-regulated in the paraventricular nucleus of the hypothalamus (PVN) at 16 h after cessation of CVS, but no other alterations in PVN CRH or arginine vasopressin mRNA expression were observed. Thus, in contrast to our hypothesis, reductions of HPA axis sensitivity to psychogenic stressors manifested at delayed recovery time points after CVS. The capacity of the HPA axis to respond to a systemic stressor appeared largely intact during recovery from CVS. These data suggest that chronic stress selectively targets brain circuits responsible for integration of psychogenic stimuli, resulting in decreased HPA axis responsiveness, possibly mediated in part by transitory alterations in PVN CRH expression.

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The effects of environmental enrichment on nicotine condition place preference in male rats.

Experimental and Clinical Psychopharmacology ◽

10.1037/pha0000024 ◽

2015 ◽

Vol 23 (5) ◽

pp. 387-394 ◽

Cited By ~ 7

Author(s):

Sarah E. Ewin ◽

Megan M. Kangiser ◽

Dustin J. Stairs

Keyword(s):

Environmental Enrichment ◽

Place Preference ◽

Male Rats

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Facilitation of the HPA Axis to a Novel Acute Stress Following Chronic Stress Exposure Modulates Histone Acetylation and the ERK/MAPK Pathway in the Dentate Gyrus of Male Rats

Endocrinology ◽

10.1210/en.2013-1918 ◽

2014 ◽

Vol 155 (8) ◽

pp. 2942-2952 ◽

Cited By ~ 21

Author(s):

Chantelle L. Ferland ◽

Erin P. Harris ◽

Mai Lam ◽

Laura A. Schrader

Keyword(s):

Dentate Gyrus ◽

Histone Acetylation ◽

Chronic Stress ◽

Hpa Axis ◽

Acute Stress ◽

Male Rats ◽

Stress Exposure ◽

Erk Activation ◽

Acute And Chronic Stress ◽

Acute Stressor

Evidence suggests that when presented with novel acute stress, animals previously exposed to chronic homotypic or heterotypic stressors exhibit normal or enhanced hypothalamic-pituitary-adrenal (HPA) response compared with animals exposed solely to that acute stressor. The molecular mechanisms involved in this effect remain unknown. The extracellular signal-regulated kinase (ERK) is one of the key pathways regulated in the hippocampus in both acute and chronic stress. The aim of this study was to examine the interaction of prior chronic stress, using the chronic variable stress model (CVS), with exposure to a novel acute stressor (2,5-dihydro-2,4,5-trimethyl thiazoline; TMT) on ERK activation, expression of the downstream protein BCL-2, and the glucocorticoid receptor co-chaperone BAG-1 in control and chronically stressed male rats. TMT exposure after chronic stress resulted in a significant interaction of chronic and acute stress in all 3 hippocampus subregions on ERK activation and BCL-2 expression. Significantly, acute stress increased ERK activation, BCL-2 and BAG-1 protein expression in the dentate gyrus (DG) of CVS-treated rats compared with control, CVS-treated alone, and TMT-only animals. Furthermore, CVS significantly increased ERK activation in medial prefrontal cortex, but acute stress had no significant effect. Inhibition of corticosterone synthesis with metyrapone had no significant effect on ERK activation in the hippocampus; therefore, glucocorticoids alone do not mediate the molecular effects. Finally, because post-translational modifications of histones are believed to play an important role in the stress response, we examined changes in histone acetylation. We found that, in general, chronic stress decreased K12H4 acetylation, whereas acute stress increased acetylation. These results indicate a molecular mechanism by which chronic stress-induced HPA axis plasticity can lead to neurochemical alterations in the hippocampus that influence reactivity to subsequent stress exposure. This may represent an important site of dysfunction that contributes to stress-induced pathology such as depression, anxiety disorders, and posttraumatic stress disorder.

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