Epigenetic mechanisms underlying learning and the inheritance of learned behaviors

Dias, Brian; Maddox, Stephanie A.; Klengel, Torsten; Ressler, Kerry J.

doi:10.1016/j.tins.2014.12.003

Cited by 109 publications

(85 citation statements)

References 88 publications

(88 reference statements)

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“…Interestingly, in that study exposure effects were identified at specific sites in both exposed mothers and offspring, and mothers' methylation correlated with offspring methylation. It is also necessary to investigate multiple generations to differentiate among exposure effects, epigenetic inheritance and social transmission (9). Animal models can provide further mechanistic understanding of how extreme stress effects mediate changes in offspring.…”

Section: Discussionmentioning

confidence: 99%

“…Biological alterations associated with PTSD, and/or other stressrelated disorders have also been observed in offspring of trauma survivors who do not themselves report trauma exposure or psychiatric disorder (3)(4)(5). Animal models have demonstrated that stress-exposure can result in epigenetic alterations in the next generation, and such mechanisms have been hypothesized to underpin vulnerability to symptoms in offspring of trauma survivors (6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

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Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation

Yehuda

Daskalakis

Bierer

et al. 2016

Biological Psychiatry

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568

359

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation

Yehuda

Daskalakis

Bierer

et al. 2016

Biological Psychiatry

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568

359

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“…These research observations are in the direction of an epigenetic explanation of inter -individual variation and long lasting effects but have to be verified in future research. (18)(19)(20) Yehudas' actual research approach (21) is very promising as it attempts to offer a global view on gene expression and gene methylation and to specify what differentiates people with PTSD and people without PTSD in order to "identify causal networks that can help diagnose PTSD and identify new treatment targets in the brain" (22).…”

Section: Resultsmentioning

confidence: 99%

Neurobiology of PTSD and implications for treatment: An overview

Sakellariou¹,

Stefanatou²

2017

Curr Res Integr Med

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T raumatic events accompany our everyday life in the form subjective painful losses and wounding: It may be the loss of a home pet, the loss of a job, robbery, a car accident, natural disasters, severe illness, the death of a beloved person, emotional neglect and abuse, betrayal, bullying, sexual abuse, rape, an earthquake, war, a terrorist attack. According to statistics one out of two persons will be exposed to a life-threatening event during lifetime (1). Some of them will be able to overcome this experience; some will be severely affected in the long term. Relevant studies indicate that about 7% of Americans have a prevalence to develop a Post-Traumatic Stress Disorder (PTSD) at some point of their lives. According to statistical data men are more often exposed to traumatic events than women, but women are more likely to suffer from a PTSD disorder (2,3). Respective data for Greece are at this time not available. Nevertheless, the refugees' crisis we are facing as a hosting country arises the issue of PTSD to a first line social problem that we have to face in terms of policy measures and treatment options. How can Neurobiology contribute to the understanding of what happens in body and mind of a person suffering from PTSD? Can neurobiological findings reveal a new perspective in the treatment of PTSD beyond pharmacotherapy and classical psychotherapeutic approaches that might contribute to develop effective psychotherapeutic interventions? What does the experience of PTSD mean for the offspring of PTSD sufferers? From a traumatic experience to PTSDExtreme stressful situations in life are addressed by an instinctive "fight or flight" response in order to assure survival. Alerting sensory environmental information reaches the brain and enters the amygdala, the operation center of the brain in the case of extreme stressful situations that is responsible for the activation of the hypothalamic -pituitary adrenal axis (HPA) and the sympathetic nervous system (SNS). This activation produces multiple effects in body and mind in order for the individual to cope with the stressors. Via the SNS system the adrenal glands release hormones called catecholamines into the blood causing increased blood pressure, glucose levels and heart rate in order to support the body to "fight or fly". At the same time the hypothalamus, when stimulated releases neuropeptides that lead to the discharge of cortisol that binds the glucocorticoid receptors in the brain and reduces stress responses (4). Usually the stress response function contributes to the adaptation to threat and restores the homeostasis of the organism with an extinction of these reactions when stimuli are not present any more. Traumatic experiences are triggered by perceived overwhelming danger and are accompanied by intense feelings of fear, horror and helplessness. Such situations may lead to a dysregulation of the described underlying biological stress mechanisms known as the "fear circuitry" leading to stress related symptoms like PTSD. The state of chemical dysregul...

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“…1D). It is notable that a large proportion of examples of non-genetic inheritance reported so far in mammals relate to carbohydrate and lipid metabolism, and brain and behavior (Choi and Mango, 2014;Bale, 2015;Sharma, 2015b;Szyf, 2015;Dias et al, 2015). In addition, a recent study has found that thousands of genes that escape genome-wide DNA demethylation in human primordial germ cells (PGCs), whose complete data set is not reported, are over-represented in genes expressed in brain, and genes associated with metabolic, and neurological and neuropsychiatric disorders .…”

Section: Resultsmentioning

confidence: 99%

Systems genomics analysis centered on epigenetic inheritance supports development of a unified theory of biology

Sharma

2015

Journal of Experimental Biology

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New discoveries are increasingly demanding integration of epigenetics, molecular biology, genomic networks and physiology with evolution. This article provides a proof of concept for evolutionary transgenerational systems biology, proposed recently in the context of epigenetic inheritance in mammals. Gene set enrichment analysis of available genome-level mammalian data presented here seem consistent with the concept that: (1) heritable information about environmental effects in somatic cells is communicated to the germline by circulating microRNAs (miRNAs) or other RNAs released in physiological fluids; (2) epigenetic factors including miRNA-like small RNAs, DNA methylation and histone modifications are propagated across generations via gene networks; and (3) inherited epigenetic variations in the form of methylated cytosines are fixed in the population as thymines over the evolutionary time course. The analysis supports integration of physiology and epigenetics with inheritance and evolution. This may catalyze efforts to develop a unified theory of biology.

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Epigenetic mechanisms underlying learning and the inheritance of learned behaviors

Cited by 109 publications

References 88 publications

Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation

Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation

Neurobiology of PTSD and implications for treatment: An overview

Systems genomics analysis centered on epigenetic inheritance supports development of a unified theory of biology

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