scholarly journals Methylation of the glucocorticoid receptor promoter in children: Links with parents as teachers, early life stress, and behavior problems

2020 ◽  
pp. 1-13
Author(s):  
Elena Silvia Gardini ◽  
Simone Schaub ◽  
Alex Neuhauser ◽  
Erich Ramseier ◽  
Arna Villiger ◽  
...  
Keyword(s):  
At Risk ◽  
Behavior Problems ◽  
Glucocorticoid Receptor ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Parents As Teachers ◽  
Cpg Site ◽  
Glucocorticoid Receptor Gene ◽  
And Behavior

Abstract The present study examined the effect of early life stress (ELS) on the glucocorticoid receptor gene (NR3C1) methylation, the associations between NR3C1 methylation and behavior problems, and the effect of the program Parents as Teachers (PAT) on NR3C1 methylation. Participants included 132 children, 72 assigned to the PAT intervention group and 60 to the PAT control group. Children were aged 3 years, and were living in psychosocially at-risk families. We assessed NR3C1 methylation of the NGFI-A binding regions of exon 1F via sodium bisulfite sequencing from saliva DNA. Results indicated that (a) children living in families receiving PAT had decreased methylation at one single cytosine–guanine dinucleotides (CpG) site; (b) current maternal depressive symptoms and parental disagreement were predictive of increased methylation of mean NGFI-A and three single CpG sites; and (c) increased methylation of mean NGFI-A and one single CpG site was significantly associated with increased internalizing and externalizing symptoms. In addition, mean NGFI-A was a mediator of the association between parental disagreement and a child's affective problems. These results suggest that PAT may contribute to preventing NR3C1 methylation in preschool children living in psychosocially at-risk situations, and confirm previous findings on the associations between ELS, NR3C1 methylation, and behavior problems.

scholarly journals DNA methylation of the glucocorticoid receptor gene predicts substance use in adolescence: longitudinal data from over 1000 young individuals

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elena Raffetti ◽  
Philippe Anastasios Melas ◽  
Anton Jonatan Landgren ◽  
Filip Andersson ◽  
Yvonne Forsell ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Substance Use ◽  
Glucocorticoid Receptor ◽  
Life Stress ◽  
Early Life ◽  
Predictor Variable ◽  
Early Life Stress ◽  
Glucocorticoid Receptor Gene ◽  
Self Reports ◽  
Middle Adolescence

AbstractEarly life stress has been linked to increased methylation of the Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) gene, which codes for the glucocorticoid receptor. Moreover, early life stress has been associated with substance use initiation at a younger age, a risk factor for developing substance use disorders. However, no studies to date have investigated whether NR3C1 methylation can predict substance use in young individuals. This study included adolescents 13–14 years of age that reported no history of substance use at baseline, (N = 1041; males = 46%). Participants contributed saliva DNA samples and were followed in middle adolescence as part of KUPOL, a prospective cohort study of 7th-grade students in Sweden. Outcome variables were self-reports of (i) recent use, (ii) lifetime use, and (iii) use duration of (a) alcohol, (b) tobacco products, (c) cannabis, or (d) any substance. Outcomes were measured annually for three consecutive years. The predictor variable was DNA methylation at the exon 1 F locus of NR3C1. Risk and rate ratios were calculated as measures of association, with or without adjustment for internalizing symptoms and parental psychiatric disorders. For a subset of individuals (N = 320), there were also morning and afternoon salivary cortisol measurements available that were analyzed in relation to NR3C1 methylation levels. Baseline NR3C1 hypermethylation associated with future self-reports of recent use and use duration of any substance, before and after adjustment for potential confounders. The overall estimates were attenuated when considering lifetime use. Sex-stratified analyses revealed the strongest association for cigarette use in males. Cortisol analyses revealed associations between NR3C1 methylation and morning cortisol levels. Findings from this study suggest that saliva NR3C1 hypermethylation can predict substance use in middle adolescence. Additional longitudinal studies are warranted to confirm these findings.

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.

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.

Early-life stress mediated modulation of adult neurogenesis and behavior

2012 ◽  
Vol 227 (2) ◽  
pp. 400-409 ◽  
Author(s):  
A. Korosi ◽  
E.F.G. Naninck ◽  
C.A. Oomen ◽  
M. Schouten ◽  
H. Krugers ◽  
...  
Keyword(s):  
Adult Neurogenesis ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
And Behavior

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.

scholarly journals Hippocampal astroglial hypertrophy in mice subjected to early life maternal deprivation

2021 ◽  
Author(s):  
Arnab Nandi ◽  
Garima Virmani ◽  
Swananda Marathe
Keyword(s):  
Immune Responses ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Stratum Radiatum ◽  
Late Adulthood ◽  
Synaptic Physiology ◽  
And Behavior

Early-life stress (ELS), including chronic deprivation of maternal care, exerts persistent life-long effects on animal physiology and behavior, and is associated with several neurodevelopmental disorders. Long-lasting changes in neuronal plasticity and electrophysiology are documented extensively in the animal models of ELS. However, the role of astroglia in the lasting effects of ELS remains elusive. Astrocytes are intricately involved in the regulation of synaptic physiology and behavior. Moreover, astrocytes play a major role in the innate and adaptive immune responses in the central nervous system (CNS). The role of immune responses and neuroinflammation in the altered brain development and persistent adverse effects of ELS are beginning to be explored. Innate immune response in the CNS is characterized by a phenomenon called astrogliosis, a process in which astrocytes undergo hypertrophy, along with changes in gene expression and function. While the immune activation and neuroinflammatory changes concomitant with ELS, or in juveniles and young adults have been reported, it is unclear whether mice subjected to ELS exhibit astrogliosis-like alterations well into late-adulthood. Here, we subjected mice to maternal separation from postnatal day 2 to day 22 and performed comprehensive morphometric analysis of hippocampal astrocytes during late-adulthood. We found that the astrocytes in the stratum radiatum region of the CA1 hippocampal subfield from maternally separated mice exhibit significant hypertrophy as late as 8 months of age, revealing the crucial changes in astrocytes that manifest long after the cessation of ELS. This study highlights the persistence of neuroinflammatory changes in mice exposed to ELS.

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