Inheritable Effect of Unpredictable Maternal Separation on Behavioral Responses in Mice

Weiss, Isabelle; Franklin, Tamara B.; Vizi, Sándor; Mansuy, Isabelle M.

doi:10.3389/fnbeh.2011.00003

Cited by 142 publications

(147 citation statements)

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“…Significance was set at 0.05. Sample size was not predetermined with a statistical method but was similar to that reported in our previous publications on the MSUS model 13,[40][41][42] .…”

Section: Methodsmentioning

confidence: 76%

“…Although paradoxical at first sight, these findings indicate that the impact of early stress can vary, probably due to differences in experimental paradigms or in the sensitivity of the models. In this respect, our MSUS paradigm is a robust and reliable manipulation that differs from classical models of early life stress such as daily maternal separation or limited bedding 39 , in that it is unpredictable and combines maternal separation with additional maternal stress 13,31,40,41 . The unpredictability prevents overcompensation by extra maternal care and more closely reproduces real-life conditions of traumatic events in humans occurring in abandonment, parental neglect and with violent or abusive parents/caretakers.…”

Section: Discussionmentioning

confidence: 99%

“…The unpredictability prevents overcompensation by extra maternal care and more closely reproduces real-life conditions of traumatic events in humans occurring in abandonment, parental neglect and with violent or abusive parents/caretakers. Our previous work has shown that MSUS induces a range of symptoms including depressive-like behaviours, deficits in social interaction, loss of behavioural control and impaired memory 13,[40][41][42] . MSUS is overall more severe than other manipulations when considered in the context of the inverted U-curve model of stress 1 .…”

Section: Discussionmentioning

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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“…Significance was set at 0.05. Sample size was not predetermined with a statistical method but was similar to that reported in our previous publications on the MSUS model 13,[40][41][42] .…”

Section: Methodsmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Early life stress in fathers improves behavioural flexibility in their offspring

et al. 2014

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“…Maternal separation in young mice not only alters the DNA methylation profile in the germline of the affected males, and their behavioural response to aversive environments, but is also associated with a modified brain gene expression in their offspring, even when these are raised under normal conditions . A corresponding transgenerational effect of early maternal separation has also been found in female mice (Weiss, Franklin, & Vizi, 2011). My group has demonstrated transgenerational, epigenetically mediated changes in behaviour in chickens as a result of both chronic stress (Lindqvist et al, 2007) and brief events of early social isolation (Goerlich, Nätt, Elfwing, Macdonald, & Jensen, 2012).…”

Section: Transgenerational Effects and Inheritance Of Epigenetic Modimentioning

confidence: 99%

Transgenerational epigenetic effects on animal behaviour

Jensen

2013

Progress in Biophysics and Molecular Biology

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Over the last decade a shift in paradigm has occurred with respect to the interaction between environment and genes. It is now clear that animal genomes are regulated to a large extent as a result of input from environmental events and experiences, which cause short-and long-term modifications in epigenetic markings of DNA and histones. In this review, the evidence that such epigenetic modifications can affect the behaviour of animals is explored, and whether such acquired behaviour alterations can transfer across generation borders. First, the mechanisms by which experiences cause epigenetic modifications are examined.This includes, for example, methylation of cytosine in CpG-positions and acetylation of histones, and studies showing that this can be modified by early experiences. Secondly, the evidence that specific modifications in the epigenome can be the cause of behaviour variation is reviewed. Thirdly, the extent to which this phenotypically active epigenetic variants can be inherited either through the germline or through reoccurring environmental conditions is examined. A particularly interesting observation is that epigenetic modifications are often linked to stress, and may possibly be mediated by steroid effects. Finally, the idea that transgenerationally stable epigenetic variants may serve as substrates for natural selection is explored, and it is speculated that they may even predispose for directed, non-random mutations.3

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“…In some models, stress exposure of the female results in transmission to the F2 generation, but only through F1 males (Morgan and Bale, 2011;Saavedra-Rodriguez and Feig, 2012), suggesting male gamete-mediated F1 to F2 transmission. Maternal separation during early postnatal development results in behavioral deficits in the F1 offspring that are transmitted to the F2 generation through females (Weiss et al, 2011). Finally, mice exposed to chronic social stress during adolescence and early adulthood exhibit persistent behavioral alterations, including enhanced anxiety and social deficits (Saavedra-Rodríguez and Feig, 2013).…”

Section: Effect Of Stress Abused Drugs and Toxins Across Generationsmentioning

confidence: 99%

Mechanisms of Non-Genetic Inheritance and Psychiatric Disorders

Tóth

2014

Neuropsychopharmacol

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Inheritance is typically associated with the Mendelian transmission of information from parents to offspring by alleles (DNA sequence). However, empirical data clearly suggest that traits can be acquired from ancestors by mechanisms that do not involve genetic alleles, referred to as non-genetic inheritance. Information that is non-genetically transmitted across generations includes parental experience and exposure to certain environments, but also parental mutations and polymorphisms, because they can change the parental 'intrinsic' environment. Non-genetic inheritance is not limited to the first generation of the progeny, but can involve the grandchildren and even further generations. Non-genetic inheritance has been observed for multiple traits including overall development, cardiovascular risk and metabolic symptoms, but this review will focus on the inheritance of behavioral abnormalities pertinent to psychiatric disorders. Multigenerational non-genetic inheritance is often interpreted as the transmission of epigenetic marks, such as DNA methylation and chromatin modifications, via the gametes (transgenerational epigenetic inheritance). However, information can be carried across generations by a large number of bioactive substances, including hormones, cytokines, and even microorganisms, without the involvement of the gametes. We reason that this broader definition of non-genetic inheritance is more appropriate, especially in the context of psychiatric disorders, because of the well-recognized role of parental and early life environmental factors in later life psychopathology. Here we discuss the various forms of non-genetic inheritance in humans and animals, as well as rodent models of psychiatric conditions to illustrate possible mechanisms.

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Inheritable Effect of Unpredictable Maternal Separation on Behavioral Responses in Mice

Cited by 142 publications

References 50 publications

Early life stress in fathers improves behavioural flexibility in their offspring

Early life stress in fathers improves behavioural flexibility in their offspring

Transgenerational epigenetic effects on animal behaviour

Mechanisms of Non-Genetic Inheritance and Psychiatric Disorders

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