A Methyl-Balanced Diet Prevents CRF-Induced Prenatal Stress-Triggered Predisposition to Binge Eating-like Phenotype

Schroêder, M.; Jakovcevski, Mira; Polacheck, Tamar; Lebow, Maya; Drori, Yonat; Engel, Mareen; Ben‐Dor, Shifra; Chen, Alon

doi:10.1016/j.cmet.2017.05.001

Cited by 33 publications

(33 citation statements)

References 61 publications

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“…Contrary to our expectations, PNS females gained similar weight ( Figure 4 B), consumed less WD during the habituation period ( Figure 4 C) when compared to CTRL group and overall did not develop BE ( Figure 4 D). Thus, the PNS females’ response appears to reflect anhedonia rather than the expected compulsivity observed in a different model of late gestational stress [15] . From a metabolic perspective, PNS females exposed to this protocol showed decreased food intake post-recovery, lowered metabolic rate, and similar activity in comparison to CTRLs ( Figure 4 E).…”

Section: Resultsmentioning

confidence: 84%

“…Interestingly, late PNS and HF diet increases adiposity in female, but not male rats [52] . Late PNS further increases susceptibility to BE in female mice [15] and to ABA in a subset of passively stress-coping female rats [52] . In contrast, when PNS takes place during the whole gestational period, the females’ innate susceptibility to ABA disappears [23] .…”

Section: Discussionmentioning

confidence: 99%

“…This enzyme, which senses changes in maternal energy homeostasis and regulates epigenetic marks on chromatin, is reduced by early gestational stress in males only and therefore may regulate sex-specific epigenetic modifications of genes important for adult metabolism [13] . In contrast, the impact of late-gestation prenatal stress on adult responsivity and metabolism appears to be more profound in females [14] , [15] , [16] .…”

Section: Introductionmentioning

confidence: 90%

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Sex dependent impact of gestational stress on predisposition to eating disorders and metabolic disease

Schroêder

Jakovcevski

Polacheck

et al. 2018

Molecular Metabolism

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ObjectiveVulnerability to eating disorders (EDs) is broadly assumed to be associated with early life stress. However, a careful examination of the literature shows that susceptibility to EDs may depend on the type, severity and timing of the stressor and the sex of the individual. We aimed at exploring the link between chronic prenatal stress and predisposition to EDs and metabolic disease.MethodsWe used a chronic variable stress protocol during gestation to explore the metabolic response of male and female offspring to food restriction (FR), activity-based anorexia (ABA), binge eating (BE) and exposure to high fat (HF) diet.ResultsContrary to controls, prenatally stressed (PNS) female offspring showed resistance to ABA and BE and displayed a lower metabolic rate leading to hyperadiposity and obesity on HF diet. Male PNS offspring showed healthy responses to FR and ABA, increased propensity to binge and improved coping with HF compared to controls. We found that long-lasting abnormal responses to metabolic challenge are linked to fetal programming and adult hypothalamic dysregulation in PNS females, resulting from sexually dimorphic adaptations in placental methylation and gene expression.ConclusionsOur results show that maternal stress may have variable and even opposing effects on ED risk, depending on the ED and the sex of the offspring.

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Section: Resultsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%

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Sex dependent impact of gestational stress on predisposition to eating disorders and metabolic disease

Schroêder

Jakovcevski

Polacheck

et al. 2018

Molecular Metabolism

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“…Exposure to prenatal stress or GCs has been associated with persisting changes in DNAm in neuronal tissues and cells. In animal models of prenatal stress, lasting changes in DNAm in the hypothalamus or hippocampus have been reported in specific candidate genes (21,22). Another set of studies has reported the impact of chronic administration of GCs on DNAm in adult mouse hippocampus as well as in a rodent primary neuronal cell line, both in candidate genes (17,23) and at a genome-wide level (18,24).…”

Section: Significancementioning

confidence: 99%

Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation

Provençal

Arloth

Cattaneo

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

151

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Prenatal stress exposure is associated with risk for psychiatric disorders later in life. This may be mediated in part via enhanced exposure to glucocorticoids (GCs), which are known to impact neurogenesis. We aimed to identify molecular mediators of these effects, focusing on long-lasting epigenetic changes. In a human hippocampal progenitor cell (HPC) line, we assessed the short- and long-term effects of GC exposure during neurogenesis on messenger RNA (mRNA) expression and DNA methylation (DNAm) profiles. GC exposure induced changes in DNAm at 27,812 CpG dinucleotides and in the expression of 3,857 transcripts (false discovery rate [FDR] ≤ 0.1 and absolute fold change [FC] expression ≥ 1.15). HPC expression and GC-affected DNAm profiles were enriched for changes observed during human fetal brain development. Differentially methylated sites (DMSs) with GC exposure clustered into 4 trajectories over HPC differentiation, with transient as well as long-lasting DNAm changes. Lasting DMSs mapped to distinct functional pathways and were selectively enriched for poised and bivalent enhancer marks. Lasting DMSs had little correlation with lasting expression changes but were associated with a significantly enhanced transcriptional response to a second acute GC challenge. A significant subset of lasting DMSs was also responsive to an acute GC challenge in peripheral blood. These tissue-overlapping DMSs were used to compute a polyepigenetic score that predicted exposure to conditions associated with altered prenatal GCs in newborn’s cord blood DNA. Overall, our data suggest that early exposure to GCs can change the set point of future transcriptional responses to stress by inducing lasting DNAm changes. Such altered set points may relate to differential vulnerability to stress exposure later in life.

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“…Thus, blocking CRH receptors modulates partner preference in prairie voles (Lim et al, 2007) and alters nicotine-use behaviors (Marcinkiewcz et al, 2009). In contrast, CRH microinjections in the NAc amplify incentive salience of Pavlovian cues for rewards in rodents (Peciña et al, 2006), a potential mechanism for stress-triggered drug relapse and stress-related binge eating (Schroeder et al, 2017). In stress-naïve rodents, microinjections of CRH into the NAc induces a conditioned place preference and increases local dopamine release (Lemos et al, 2012).…”

mentioning

confidence: 99%

New viral‐genetic mapping uncovers an enrichment of corticotropin‐releasing hormone‐expressing neuronal inputs to the nucleus accumbens from stress‐related brain regions

Itoga

Chen

Fateri

et al. 2019

J of Comparative Neurology

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Corticotropin‐releasing hormone (CRH) is an essential, evolutionarily‐conserved stress neuropeptide. In addition to hypothalamus, CRH is expressed in brain regions including amygdala and hippocampus where it plays crucial roles in modulating the function of circuits underlying emotion and cognition. CRH+ fibers are found in nucleus accumbens (NAc), where CRH modulates reward/motivation behaviors. CRH actions in NAc may vary by the individual's stress history, suggesting roles for CRH in neuroplasticity and adaptation of the reward circuitry. However, the origin and extent of CRH+ inputs to NAc are incompletely understood. We employed viral genetic approaches to map both global and CRH+ projection sources to NAc in mice. We injected into NAc variants of a new designer adeno‐associated virus that permits robust retrograde access to NAc‐afferent projection neurons. Cre‐dependent viruses injected into CRH‐Cre mice enabled selective mapping of CRH+ afferents. We employed anterograde AAV1‐directed axonal tracing to verify NAc CRH+ fiber projections and established the identity of genetic reporter‐labeled cells via validated antisera against native CRH. We quantified the relative contribution of CRH+ neurons to total NAc‐directed projections. Combined retrograde and anterograde tracing identified the paraventricular nucleus of the thalamus, bed nucleus of stria terminalis, basolateral amygdala, and medial prefrontal cortex as principal sources of CRH+ projections to NAc. CRH+ NAc afferents were selectively enriched in NAc‐projecting brain regions involved in diverse aspects of the sensing, processing and memory of emotionally salient events. These findings suggest multiple, complex potential roles for the molecularly‐defined, CRH‐dependent circuit in modulation of reward and motivation behaviors.

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A Methyl-Balanced Diet Prevents CRF-Induced Prenatal Stress-Triggered Predisposition to Binge Eating-like Phenotype

Cited by 33 publications

References 61 publications

Sex dependent impact of gestational stress on predisposition to eating disorders and metabolic disease

Sex dependent impact of gestational stress on predisposition to eating disorders and metabolic disease

Glucocorticoid exposure during hippocampal neurogenesis primes future stress response by inducing changes in DNA methylation

New viral‐genetic mapping uncovers an enrichment of corticotropin‐releasing hormone‐expressing neuronal inputs to the nucleus accumbens from stress‐related brain regions

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