Long-term effects of early life stress exposure: Role of epigenetic mechanisms

Silberman, Dafne M.; Acosta, Gabriela Beatriz; Zubilete, Marı́a Aurelia Zorrilla

doi:10.1016/j.phrs.2015.12.033

Cited by 83 publications

(47 citation statements)

References 180 publications

(200 reference statements)

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“…Secondly, ELS may induce modifications of the epigenome which lastingly affect brain function (Babenko et al, 2015). Briefly, epigenetics refers to mechanisms by which the environment interacts with the genome by the modification of chromatin structure or control of mRNA translation (Silberman et al, 2016). DNA methylation, post-translational histone modifications (methylation, phosphorylation, acetylation) and noncoding RNA activity are among the most studied epigenetic mechanisms that regulate gene expression.…”

Section: Hpa-axis Programming By Early Life Stress (Els)mentioning

confidence: 99%

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

Bodegom

Homberg

Henckens

2017

Front. Cell. Neurosci.

445

331

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Exposure to stress during critical periods in development can have severe long-term consequences, increasing overall risk on psychopathology. One of the key stress response systems mediating these long-term effects of stress is the hypothalamic-pituitary-adrenal (HPA) axis; a cascade of central and peripheral events resulting in the release of corticosteroids from the adrenal glands. Activation of the HPA-axis affects brain functioning to ensure a proper behavioral response to the stressor, but stress-induced (mal)adaptation of the HPA-axis' functional maturation may provide a mechanistic basis for the altered stress susceptibility later in life. Development of the HPA-axis and the brain regions involved in its regulation starts prenatally and continues after birth, and is protected by several mechanisms preventing corticosteroid over-exposure to the maturing brain. Nevertheless, early life stress (ELS) exposure has been reported to have numerous consequences on HPA-axis function in adulthood, affecting both its basal and stress-induced activity. According to the match/mismatch theory, encountering ELS prepares an organism for similar (“matching”) adversities during adulthood, while a mismatching environment results in an increased susceptibility to psychopathology, indicating that ELS can exert either beneficial or disadvantageous effects depending on the environmental context. Here, we review studies investigating the mechanistic underpinnings of the ELS-induced alterations in the structural and functional development of the HPA-axis and its key external regulators (amygdala, hippocampus, and prefrontal cortex). The effects of ELS appear highly dependent on the developmental time window affected, the sex of the offspring, and the developmental stage at which effects are assessed. Albeit by distinct mechanisms, ELS induced by prenatal stressors, maternal separation, or the limited nesting model inducing fragmented maternal care, typically results in HPA-axis hyper-reactivity in adulthood, as also found in major depression. This hyper-activity is related to increased corticotrophin-releasing hormone signaling and impaired glucocorticoid receptor-mediated negative feedback. In contrast, initial evidence for HPA-axis hypo-reactivity is observed for early social deprivation, potentially reflecting the abnormal HPA-axis function as observed in post-traumatic stress disorder, and future studies should investigate its neural/neuroendocrine foundation in further detail. Interestingly, experiencing additional (chronic) stress in adulthood seems to normalize these alterations in HPA-axis function, supporting the match/mismatch theory.

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Section: Hpa-axis Programming By Early Life Stress (Els)mentioning

confidence: 99%

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

Bodegom

Homberg

Henckens

2017

Front. Cell. Neurosci.

445

331

View full text Add to dashboard Cite

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“…; Silberman et al . ). Exposure to heat stress during the critical period of thermal‐control establishment (between days 3 and 5 post‐hatch) in chicks causes long‐lasting alterations that contribute to a differential response to subsequent related stimuli (Kisliouk et al .…”

mentioning

confidence: 97%

“…; Silberman et al . ). Recent studies have shown that heat shock induces a series of epigenetic modifications, providing evidence for the existence of a heat‐stress‐related histone code (Fritah et al .…”

mentioning

confidence: 97%

Methyl CpG level at distal part of heat‐shock protein promoter HSP70 exhibits epigenetic memory for heat stress by modulating recruitment of POU2F1‐associated nucleosome‐remodeling deacetylase (NuRD) complex

Kisliouk

Cramer

Meiri

2017

Journal of Neurochemistry

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Depending on its stringency, exposure to heat in early life leads to either resilience or vulnerability to heat stress later in life. We hypothesized that epigenetic alterations in genes belonging to the cell proteostasis pathways are attributed to long-term responses to heat stress. Epigenetic regulation of the mRNA expression of the molecular chaperone heat-shock protein (HSP) 70 (HSPA2) was evaluated in the chick hypothalamus during the critical period of thermal-control establishment on day 3 post-hatch and during heat challenge on day 10. Both the level and duration of HSP70 expression during heat challenge a week after heat conditioning were more pronounced in chicks conditioned under harsh versus mild temperature. Analyzing different segments of the promoter in vitro indicated that methylation of a distal part altered its transcriptional activity. In parallel, DNA-methylation level of this segment in vivo was higher in harsh- compared to mild-heat-conditioned chicks. Hypermethylation of the HSP70 promoter in high-temperature-conditioned chicks was accompanied by a reduction in both POU Class 2 Homeobox 1 (POU2F1) binding and recruitment of the nucleosome remodeling deacetylase (NuRD) chromatin-remodeling complex. As a result, histone H3 acetylation levels at the HSP70 promoter were higher in harsh-temperature-conditioned chicks than in their mild-heat-conditioned counterparts. These results suggest that methylation level of a distal part of the HSP70 promoter and POU2F1 recruitment may reflect heat-stress-related epigenetic memory and may be useful in differentiating between individuals that are resilient or vulnerable to stress.

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“…Preclinical studies have shown that ELS leads to persistent changes in neural structure and depression‐like behavior during adulthood . Recent findings suggest that these changes can be attributed to epigenetic modifications in chromatin remodeling induced by environmental factors, such as ELS . Such modifications cause long‐lasting effects on gene expression and neural plasticity …”

mentioning

confidence: 99%

Effects of maternal separation and antidepressant drug on epigenetic regulation of the brain‐derived neurotrophic factor exon I promoter in the adult rat hippocampus

Park

Seo

Lee

et al. 2017

Psychiatry Clin Neurosci

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Long-term effects of early life stress exposure: Role of epigenetic mechanisms

Cited by 83 publications

References 180 publications

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure

Methyl CpG level at distal part of heat‐shock protein promoter HSP70 exhibits epigenetic memory for heat stress by modulating recruitment of POU2F1‐associated nucleosome‐remodeling deacetylase (NuRD) complex

Effects of maternal separation and antidepressant drug on epigenetic regulation of the brain‐derived neurotrophic factor exon I promoter in the adult rat hippocampus

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