scholarly journals The role of glucocorticoid receptor-dependent activity in the amygdala central nucleus and reversibility of early-life stress programmed behavior

2015 ◽  
Vol 5 (4) ◽  
pp. e542-e542 ◽  
Author(s):  
M G Arnett ◽  
M S Pan ◽  
W Doak ◽  
P E P Cyr ◽  
L M Muglia ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Central Nucleus ◽  
Dependent Activity

scholarly journals Sexual dimorphic role of the glucocorticoid receptor in chronic muscle pain produced by early-life stress

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine
Keyword(s):  
Glucocorticoid Receptor ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Glucocorticoid Receptors ◽  
Early Life Stress ◽  
Nociceptive Threshold ◽  
Male And Female ◽  
Mechanical Nociceptive Threshold

Fibromyalgia and other chronic musculoskeletal pain syndromes are associated with stressful early life events, which can produce a persistent dysregulation in the hypothalamic-pituitary adrenal (HPA) stress axis function, associated with elevated plasm levels of corticosterone in adults. To determine the contribution of the HPA axis to persistent muscle hyperalgesia in adult rats that had experienced neonatal limited bedding (NLB), a form of early-life stress, we evaluated the role of glucocorticoid receptors on muscle nociceptors in adult NLB rats. In adult male and female NLB rats, mechanical nociceptive threshold in skeletal muscle was significantly lower than in adult control (neonatal standard bedding) rats. Furthermore, adult males and females that received exogenous corticosterone (via dams’ milk) during postnatal days 2–9, displayed a similar lowered mechanical nociceptive threshold. To test the hypothesis that persistent glucocorticoid receptor signaling in the adult contributes to muscle hyperalgesia in NLB rats, nociceptor expression of glucocorticoid receptor (GR) was attenuated by spinal intrathecal administration of an oligodeoxynucleotide (ODN) antisense to GR mRNA. In adult NLB rats, GR antisense markedly attenuated muscle hyperalgesia in males, but not in females. These findings indicate that increased corticosterone levels during a critical developmental period (postnatal days 2–9) produced by NLB stress induces chronic mechanical hyperalgesia in male and female rats that persists in adulthood, and that this chronic muscle hyperalgesia is mediated, at least in part, by persistent stimulation of glucocorticoid receptors on sensory neurons, in the adult male, but not female rat.

The Role of Early Life Stress in HPA Axis and Anxiety

2020 ◽  
pp. 141-153 ◽  
Author(s):  
Mario F. Juruena ◽  
Filip Eror ◽  
Anthony J. Cleare ◽  
Allan H. Young
Keyword(s):  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress

scholarly journals Effects of Early Life Stress on Epigenetic Changes of the Glucocorticoid Receptor 17 Promoter during Adulthood

2020 ◽  
Vol 21 (17) ◽  
pp. 6331
Author(s):  
Mi Kyoung Seo ◽  
Seon-gu Kim ◽  
Dae-Hyun Seog ◽  
Won-Myong Bahk ◽  
Seong-Ho Kim ◽  
...  
Keyword(s):  
Young Adult ◽  
Glucocorticoid Receptor ◽  
Histone Modification ◽  
Life Span ◽  
Histone Acetylation ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Epigenetic Changes ◽  
Immobility Time

Growing evidence suggests that early life stress (ELS) has long-lasting effects on glucocorticoid receptor (GR) expression and behavior via epigenetic changes of the GR exon 17 promoter. However, it remains unclear whether ELS regulates histone modifications of the GR exon 17 promoter across the life span. We investigated the effects of maternal separation (MS) on histone acetylation and methylation of GR exon 17 promoter in the hippocampus, according to the age of adults. Depression-like behavior and epigenetic regulation of GR expression were examined at young and middle adulthood in mice subjected to MS from postnatal day 1 to 21. In the forced swimming test, young adult MS mice showed no effect on immobility time, but middle-aged MS mice significantly increased immobility time. Young adult and middle-aged MS mice showed decreased GR expression. Their two ages showed decreased histone acetylation with increased histone deacetylases (HDAC5) levels, decreased permissive methylation, and increased repressive methylation at the GR exon 17 promoter. The extent of changes in gene expression and histone modification in middle adulthood was greater than in young adulthood. These results indicate that MS in early life causes long-term negative effects on behavior via histone modification of the GR gene across the life span.

Neurodevelopmental plasticity and psychiatric vulnerability

2015 ◽  
Vol 30 (S2) ◽  
pp. S70-S70
Author(s):  
A. Dayer
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Methylation Status ◽  
Early Life Stress ◽  
Childhood Adversity ◽  
Cellular Level ◽  
Special Focus ◽  
Serotonin System ◽  
Increase Risk

The early developmental period is characterized by a high degree of plasticity and, consequently, is very sensitive to environmental factors, such as early life stressors (ELS). Exposure to ELS is known to increase risk to psychopathologies such as depression and anxiety disorders later in life . At a cellular level, alterations in the migration and integration of GABAergic interneurons (INs) in cortical circuits have emerged as a key processes involved in the vulnerability to psychiatric disorders . In humans and rodents, ELS interacts with genes regulating the serotonin system to increase risk to stress-related disorders . In addition, ELS is associated to a variety of epigenetic methylation changes in blood DNA from patients displaying a high loading of ELS . Here, we aimed to investigate the role of the ionotropic serotonin 3A receptor (5-HT3AR) at a genetic and epigenetic level in rodent and human models of early-life stress. We will first present data indicating that the 5-HT3AR is specifically expressed in a subset of cortical INs derived from the caudal ganglionic eminence (CGE) and controls early steps of cortical circuit assembly . Interestingly, the migration, transcriptional programs and positioning of 5-HT3AR expressing interneuron subtypes were found to be dysregulated in pathological models of early-life serotonin dysregulation. At a behavioral level, we found that ELS interacts with the 5-HTR3A to modulate social behaviors. Finally, we will present human data indicating that childhood adversity significantly impacts the methylation status of the promoter region of the human 5-HT3AR in an allele-specific manner. Taken together, this presentation will highlight the importance of the serotonin system in early life development and psychopathology with a special focus on the role of the 5-HT3AR in cortical interneuron development.

Cytokines during acute abstinence of crack cocaine: The role of early life stress

2015 ◽  
Vol 146 ◽  
pp. e127
Author(s):  
Rodrigo Grassi-Oliveira ◽  
Mateus L. Levandowski ◽  
Thiago W. Viola ◽  
Luiz E. Wearick ◽  
Julio Carlos Pezzi ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Crack Cocaine ◽  
Early Life Stress

Riluzole Normalizes Early-Life Stress-Induced Visceral Hypersensitivity in Rats: Role of Spinal Glutamate Reuptake Mechanisms

2010 ◽  
Vol 138 (7) ◽  
pp. 2418-2425 ◽  
Author(s):  
Romain–Daniel Gosselin ◽  
Richard M. O'Connor ◽  
Monica Tramullas ◽  
Marcela Julio–Pieper ◽  
Timothy G. Dinan ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Visceral Hypersensitivity

Assessment of the hypothalamic–pituitary–adrenal axis activity: glucocorticoid receptor and mineralocorticoid receptor function in depression with early life stress – a systematic review

2012 ◽  
Vol 24 (1) ◽  
pp. 4-15 ◽  
Author(s):  
Cristiane Von Werne Baes ◽  
Sandra M. de Carvalho Tofoli ◽  
Camila Maria S. Martins ◽  
Mario F. Juruena
Keyword(s):  
Systematic Review ◽  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Life Stress ◽  
Early Life ◽  
Mineralocorticoid Receptor ◽  
Early Life Stress ◽  
Hypothalamic Pituitary Adrenal ◽  
Depressed Patients ◽  
Suppression Test

Objective:The mechanisms involved in the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, especially in the functioning of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in depressed patients, are not well elucidated. The objective of this study was to conduct a systematic review of articles that assess the HPA axis activity from GR and MR in depressed patients and healthy controls with or without early life stress.Methods:We conducted a systematic review of articles in PubMed, SCOPUS and SciELO published between 2000 and 2011, using the following search terms:child abuse,depression,HPA axis,dexamethasone,prednisolone,fludrocortisoneandspironolactone. Thirty-four papers were selected for this review.Results:Most studies identified in this review used the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test. In these studies, hypercortisolaemia was associated with depression. We identified three studies with the Prednisolone suppression test, only one study with the use of fludrocortisone and one with spironolactone. This review found nine studies that evaluated the HPA axis in individuals with early life stress.Conclusions:The majority of the studies assessed in this review show that early life stress leads to permanent changes in the HPA axis and may lead to development of depression in adults. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolaemia and reduced inhibitory feedback. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between GR and MR. Evidences have consistently showed that GR function is impaired in major depression, but few studies have assessed the activity of MR in depression and early life stress.

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