Epigenetic Transmission of the Impact of Early Stress Across Generations

Franklin, Tamara B.; Russig, Holger; Weiss, Isabelle; Gräff, Johannes; Linder, Natacha; Michalon, Aubin; Vizi, Sándor; Mansuy, Isabelle M.

doi:10.1016/j.biopsych.2010.05.036

Cited by 989 publications

(906 citation statements)

References 65 publications

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“…We used MSUS 13 to examine whether traumatic stress in postnatal life can have behavioural benefits in the offspring of mice. Secondgeneration (F2) offspring were obtained by breeding males, subjected to MSUS when pups or control males (F1), to wild-type C57BL/6 adult females ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Using a model of unpredictable maternal separation and maternal stress (MSUS) in mice 13 , we examined whether trauma exposure in postnatal life can have beneficial effects on behaviour in the offspring. This model aims at mimicking real-life conditions in humans that can occur in disrupted families with unpredictable and unreliable parental care, parental neglect and disorganized and poor affective attachment.…”

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confidence: 99%

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Early life stress in fathers improves behavioural flexibility in their offspring

et al. 2014

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Traumatic experiences in childhood can alter behavioural responses and increase the risk for psychopathologies across life, not only in the exposed individuals but also in their progeny. In some conditions, such experiences can however be beneficial and facilitate the appraisal of adverse environments later in life. Here we expose newborn mice to unpredictable maternal separation combined with unpredictable maternal stress (MSUS) for 2 weeks and assess the impact on behaviour in the offspring when adult. We show that MSUS in male mice favours goal-directed behaviours and behavioural flexibility in the adult offspring. This effect is accompanied by epigenetic changes involving histone post-translational modifications at the mineralocorticoid receptor (MR) gene and decreased MR expression in the hippocampus. Mimicking these changes pharmacologically in vivo reproduces the behavioural phenotype. These findings highlight the beneficial impact that early adverse experiences can have in adulthood, and the implication of epigenetic modes of gene regulation.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Early life stress in fathers improves behavioural flexibility in their offspring

et al. 2014

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“…Changes in diet, for example, are correlated with mortality of grandprogeny in humans (5), altered metabolism of progeny in mice (6), and longevity of descendants in the worm Caenorhabditis elegans (7). Maternal separation (8), social defeat (9), and chronic variable stress (10) are correlated with hypersensitivity to similar stresses in descendants in mice. Molecules that transmit gene regulatory information from one generation to the next generation in response to somatic cells that experience the effects of diet or stress could provide a mechanistic explanation for the observed correlations.…”

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confidence: 99%

Extracellular RNA is transported from one generation to the next in Caenorhabditis elegans

Marre

Traver

Jose

2016

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

107

144

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Experiences during the lifetime of an animal have been proposed to have consequences for subsequent generations. Although it is unclear how such intergenerational transfer of information occurs, RNAs found extracellularly in animals are candidate molecules that can transfer gene-specific regulatory information from one generation to the next because they can enter cells and regulate gene expression. In support of this idea, when double-stranded RNA (dsRNA) is introduced into some animals, the dsRNA can silence genes of matching sequence and the silencing can persist in progeny. Such persistent gene silencing is thought to result from sequencespecific interaction of the RNA within parents to generate chromatin modifications, DNA methylation, and/or secondary RNAs, which are then inherited by progeny. Here, we show that dsRNA can be directly transferred between generations in the worm Caenorhabditis elegans. Intergenerational transfer of dsRNA occurs even in animals that lack any DNA of matching sequence, and dsRNA that reaches progeny can spread between cells to cause gene silencing. Surprisingly, extracellular dsRNA can also reach progeny without entry into the cytosol, presumably within intracellular vesicles. Fluorescently labeled dsRNA is imported from extracellular space into oocytes along with yolk and accumulates in punctate structures within embryos. Subsequent entry into the cytosol of early embryos causes gene silencing in progeny. These results demonstrate the transport of extracellular RNA from one generation to the next to regulate gene expression in an animal and thus suggest a mechanism for the transmission of experience-dependent effects between generations.circulating RNA | parental RNAi | epigenetics | transgenerational inheritance | endocytosis

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“…Behavioral changes caused by neonatal [47] or adult [48] exposure to stress have been recently reported again, confirming that stress-induced changes are inheritable.…”

Section: Reduced Pfc Da Signaling As An Environmental Adaptation Stramentioning

confidence: 55%

“…It appears that the inheritance of these environmentallyinduced (or acquired) phenotypes involves epigenetic mechanisms [47,48] . Since these studies have followed two or three generations at most, it is still unclear whether such stress-induced epigenetic changes can be translated into equivalent genetic changes for inheritance across generations.…”

Section: Reduced Pfc Da Signaling As An Environmental Adaptation Stramentioning

confidence: 99%

Prefrontal cortical dopamine from an evolutionary perspective

Lee

Goto

2015

Neurosci. Bull.

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In this article, we propose the hypothesis that the prefrontal cortex (PFC) acquired neotenic development as a consequence of mesocortical dopamine (DA) innervation, which in turn drove evolution of the PFC into becoming a complex functional system. Accordingly, from the evolutionary perspective, decreased DA signaling in the PFC associated with such adverse conditions as chronic stress may be considered as an environmental adaptation strategy. Psychiatric disorders such as schizophrenia and attention deficit/hyperactivity disorder may also be understood as environmental adaptation or a by-product of such a process that has emerged through evolution in humans. To investigate the evolutionary perspective of DA signaling in the PFC, domestic animals such as dogs may be a useful model.

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Epigenetic Transmission of the Impact of Early Stress Across Generations

Cited by 989 publications

References 65 publications

Early life stress in fathers improves behavioural flexibility in their offspring

Early life stress in fathers improves behavioural flexibility in their offspring

Extracellular RNA is transported from one generation to the next in Caenorhabditis elegans

Prefrontal cortical dopamine from an evolutionary perspective

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