Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively

Pillai, Anup G.; Arp, Marit; Velzing, Els H.; Lesuis, Sylvie L.; Schmidt, Mathias; Holsboer, Florian; Joëls, Marian; Krugers, Harm J.

doi:10.1016/j.neuropharm.2018.02.001

Cited by 38 publications

(25 citation statements)

References 60 publications

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“…Exposure to stress and adversity as well as a western diet both alter glucocorticoid receptor levels in the hippocampus (Ke et al, 2010; Khazen, Hatoum, Ferreira, & Maroun, 2019; Szymanska et al, 2009). Interestingly, increased hippocampal glucocorticoid levels are associated with impaired cognitive function (Arp et al, 2016; Pillai et al, 2018). This is due in‐part to the regulation of hippocampal function through hippocampal glucocorticoid receptor (Zhang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Adverse maternal environment and western diet impairs cognitive function and alters hippocampal glucocorticoid receptor promoter methylation in male mice

Sterrett

et al. 2020

Physiol Rep

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Adverse maternal environment (AME) and high-fat diet in early childhood increase the risk of cognitive impairment and depression later in life. Cognitive impairment associates with hippocampal dysfunction. A key regulator of hippocampal function is the glucocorticoid receptor. Increased hippocampal GR expression associates with cognitive impairment and depression. Transcriptional control of GR relies in part upon the DNA methylation status at multiple alternative initiation sites that are tissue specific, with exon 1.7 being hippocampal specific. Increased exon 1.7 expression associates with upregulated hippocampal GR expression in early life stress animal models. However, the effects of AME combined with postweaning western diet (WD) on offspring behaviors and the expression of GR exon 1 variants in the hippocampus are unknown. We hypothesized that AME and postweaning WD would impair cognitive function and cause depression-like behavior in offspring in conjunction with dysregulated hippocampal expression of total GR and exon 1.7 variant in mice. We found that AME-WD impaired learning and memory in male adult offspring concurrently with increased hippocampal expression of total GR and GR 1.7. We also found that increased GR 1.7 expression was associated with decreased DNA methylation at the GR 1.7 promoter. We speculate that decreased DNA methylation at the GR 1.7 promoter plays a role in AME-WD induced increase of GR in the hippocampus. This increased GR expression may subsequently contribute to hippocampus dysfunction and lead to the cognitive impairment seen in this model. K E Y W O R D Sadverse maternal environment, DNA methylation, GR, hippocampus, western diet the Clinical and Translational Research Core Lab in the

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Section: Introductionmentioning

confidence: 99%

Adverse maternal environment and western diet impairs cognitive function and alters hippocampal glucocorticoid receptor promoter methylation in male mice

Sterrett

et al. 2020

Physiol Rep

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“…In addition to the initial gestational alcohol exposure, exposure to early life stress increases the risk of behavioral deficits, including adult psychiatric disorders (Kisely et al, 2018). Early life stress has a negative effect on learning and memory processes governed by the hippocampus in rodents (Rice et al, 2008;Oomen et al, 2010;Pillai et al, 2018). Little is known about how early life stress may affect children born with FASD (Price et al, 2017), although following gestational alcohol exposure and abuse or neglect during early development, children are more likely to have behavioral deficits, including impaired learning and memory (Coggins et al, 2007;Henry et al, 2007;Koponen et al, 2009;Koponen et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Hippocampal DNA Methylation in a Mouse Model of Fetal Alcohol Spectrum Disorder That Includes Maternal Separation Stress Only Partially Explains Changes in Gene Expression

Alberry

Singh

2020

Front. Genet.

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Fetal alcohol spectrum disorder (FASD) is characterized by developmental and behavioral deficits caused by maternal drinking during pregnancy. Children born with FASD often face additional stresses, including maternal separation, that add yet additional deficits. The mechanism associated with this interaction is not known. We have used a mouse model for prenatal ethanol exposure and maternal separation to demonstrate that the combination of the two treatments results in more than additive deficits. Furthermore, the behavioral deficits are associated with changes in hippocampal gene expression that persist into adulthood. What initiates and maintains these changes remains to be established and forms the focus of this report. Specifically, MeDIP-Seq was used to assess if changes in promoter DNA methylation are affected by exposure to prenatal ethanol and maternal separation including its relationship to gene expression. The novel results show that different sets of genes implicated by promoter DNA methylation are affected by both treatments independently, and a relatively unique set of genes are affected by the combination of the two treatments. Prenatal ethanol exposure leads to altered promoter DNA methylation at genes important for transcriptional regulation. Maternal separation leads to changes at genes important for histone methylation and immune response, and the combination of two treatments results in DNA methylation changes at genes important for neuronal migration and immune response. Our dual results from the same hippocampal samples suggest there is minimal complementarity between changes in promoter DNA methylation and gene expression, although genes involved tend to be critical for brain development and function. While remaining to be validated, such results argue that mechanisms beyond promoter DNA methylation must be involved in lasting gene expression alterations leading to behavioral deficits implicated in FASD. They may facilitate early and reliable diagnosis, as well as novel strategies for the amelioration of FASD-related deficits.

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“…The current study uses the limited-bedding paradigm to investigate molecular and functional adaptations to ELS in juveniles and adults. We focus on the hippocampus, based on documented sensitivity to ELS in humans and various animal models (Delpech et al, 2016;Derks et al, 2016;Hanson et al, 2015;Pillai et al, 2018;Suri and Vaidya, 2015;Teicher et al, 2018;Wei et al, 2014;Wei et al, 2015), and the wealth of anatomical and physiological data generated using this ELS paradigm (Brunson et al, 2005;Fenoglio et al, 2006;Heun-Johnson and Levitt, 2017;Ivy et al, 2010;Lesuis et al, 2019;Maniam et al, 2016;Molet et al, 2016;Naninck et al, 2015;Naninck et al, 2017;Rice et al, 2008;Walker et al, 2017;Wang et al, 2011b;Yam et al, 2019;Youssef et al, 2019). We first used an unbiased discovery approach to identify age-selective changes in the non-nuclear hippocampal proteome in juveniles and young adulthood.…”

Section: Introductionmentioning

confidence: 99%

Proteomic and mitochondrial adaptations to early-life stress are distinct in juveniles and adults

Eagleson

Villaneuva

Southern

et al. 2020

Preprint

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Exposure to early-life stress (ELS) increases risk for poor mental and physical health outcomes that emerge at different stages across the lifespan. Yet, how age interacts with ELS to impact the expression of specific phenotypes remains largely unknown. An established limited-bedding paradigm was used to induce ELS in mouse pups over the early postnatal period. Initial analyses focused on the hippocampus, based on documented sensitivity to ELS in humans and various animal models, and the large body of data reporting anatomical and physiological outcomes in this structure using this ELS paradigm. An unbiased discovery proteomics approach revealed distinct adaptations in the non-nuclear hippocampal proteome in male versus female offspring at two distinct developmental stages: juvenile and adult. Gene ontology and KEGG pathway analyses revealed significant enrichment in proteins associated with mitochondria and the oxidative phosphorylation (OXPHOS) pathway in response to ELS in female hippocampus only. To determine whether the protein adaptations to ELS reflected altered function, mitochondrial respiration (driven through complexes II-IV) and complex I activity were measured in isolated hippocampal mitochondria using a Seahorse X96 Flux analyzer and immunocapture ELISA, respectively. ELS had no effect on basal respiration in either sex at either age. In contrast, ELS increased OXPHOS capacity in juvenile males and females, and reduced OXPHOS capacity in adult females but not adult males. A similar pattern of ELS-induced changes was observed for complex I activity. These data suggest that initial adaptations in juvenile hippocampus due to ELS were not sustained in adults. Mitochondrial adaptations to ELS were also exhibited peripherally by liver. Overall, the temporal distinctions in mitochondrial responses to ELS show that ELS-generated adaptations and outcomes are complex over the lifespan. This may contribute to differences in the timing of appearance of mental and physical disturbances, as well as potential sex differences that influence only select outcomes.

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Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively

Cited by 38 publications

References 60 publications

Adverse maternal environment and western diet impairs cognitive function and alters hippocampal glucocorticoid receptor promoter methylation in male mice

Adverse maternal environment and western diet impairs cognitive function and alters hippocampal glucocorticoid receptor promoter methylation in male mice

Hippocampal DNA Methylation in a Mouse Model of Fetal Alcohol Spectrum Disorder That Includes Maternal Separation Stress Only Partially Explains Changes in Gene Expression

Proteomic and mitochondrial adaptations to early-life stress are distinct in juveniles and adults

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