Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment

Oh, Junseo; Chambwe, Nyasha; Klein, Shifra Liba; Gál, János; Andrews, Simon; Gleason, Georgia; Shaknovich, Rita; Melnick, Ari; Campagne, Fabien; Tóth, Miklós

doi:10.1038/tp.2012.130

Cited by 42 publications

(34 citation statements)

References 69 publications

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“…In more detail, the negative feedback of the HPA axis, which is required for a timely termination of the stress response, is strengthened by higher NR3C1 expression. Similar studies in animal models support the idea that methylation could be a key modulator of the stress response after early‐life adversity (Fagiolini, Jensen, & Champagne, ; Murgatroyd et al, ; Oh et al, ). Even more surprising are first indicators for changes of DNA methylation in germline cells, suggesting transgenerational effects of early‐life adversity, as persistent and maintained across generations.…”

Section: Epigenetic Processes May Account For the Long‐lasting Conseqsupporting

confidence: 60%

Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment

Ramo-Fernández

Schneider

Wilker

et al. 2015

Behavioral Sci & The Law

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Survivors of war trauma or childhood maltreatment are at increased risk for traumaspectrum disorders such as post-traumatic stress disorder (PTSD). In addition, traumatic stress has been associated with alterations in the neuroendocrine and the immune system, enhancing the risk for physical diseases. Traumatic experiences might even affect psychological as well as biological parameters in the next generation, i.e. traumatic stress might have transgenerational effects. This article outlines how epigenetic processes, which represent a pivotal biological mechanism for dynamic adaptation to environmental challenges, might contribute to the explanation of the long-lasting and transgenerational effects of trauma. In particular, epigenetic alterations in genes regulating the hypothalamus-pituitary-adrenal axis as well as the immune system have been observed in survivors of childhood and adult trauma. These changes could result in enduring alterations of the stress response as well as the physical health risk. Furthermore, the effects of parental trauma could be transmitted to the next generation by parental distress and the pre-and postnatal environment, as well as by epigenetic marks transmitted via the germline. While epigenetic research has a high potential of advancing our understanding of the consequences of trauma, the findings have to be interpreted with caution, as epigenetics only represent one piece of a complex puzzle of interacting biological and environmental factors.

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Section: Epigenetic Processes May Account For the Long‐lasting Conseqsupporting

confidence: 60%

Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment

Ramo-Fernández

Schneider

Wilker

et al. 2015

Behavioral Sci & The Law

View full text Add to dashboard Cite

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“…In contrast, rodents classified as vulnerable or resilient based on behavioral responses to acute unavoidable stress exhibited differential regulation of distinct genes, with upregulation of neuroendocrine-related genes, growth hormone, and prolactin genes in vulnerable rats, and the downregulation of interferon-β and leukemia inhibitory factor in the frontal cortex of resilient rats (Benatti et al, 2012). Furthermore, Oh et al (2013) found that an adverse maternal environment in rodents was associated with differentially methylated sites that clustered in the bodies of genes associated with cell adhesion and neurotransmitter receptors in the hippocampus. Finally, a study investigating the effects of environmental stress in non-human primates found an association between increased stress reactivity and higher overall methylation (Kinnally et al, 2011), which led them to speculate that the overall increase in methylation constrained plasticity through gene repression.…”

Section: Gene × Environment × Epigenome Interactionsmentioning

confidence: 99%

Interindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD

Zovkic¹,

Meadows²,

Kaas³

et al. 2013

Front. Psychiatry

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Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by intrusive and persistent memories of a psychologically traumatic event that leads to significant functional and social impairment in affected individuals. The molecular bases underlying persistent outcomes of a transient traumatic event have remained elusive for many years, but recent studies in rodents have implicated epigenetic modifications of chromatin structure and DNA methylation as fundamental mechanisms for the induction and stabilization of fear memory. In addition to mediating adaptations to traumatic events that ultimately cause PTSD, epigenetic mechanisms are also involved in establishing individual differences in PTSD risk and resilience by mediating long-lasting effects of genes and early environment on adult function and behavior. In this review, we discuss the current evidence for epigenetic regulation of PTSD in human studies and in animal models and comment on ways in which these models can be expanded. In addition, we identify key outstanding questions in the study of epigenetic mechanisms of PTSD in the context of rapidly evolving technologies that are constantly updating and adjusting our understanding of epigenetic modifications and their functional roles. Finally, we discuss the potential application of epigenetic approaches in identifying markers of risk and resilience that can be utilized to promote early intervention and develop therapeutic strategies to combat PTSD after symptom onset.

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“…This nongenetic maternal transmission of anxiety to wild-type mice appears to involve altered immune function in the offspring, resulting in reduced ventral hippocampal function, associated with altered DNA methylation and expression of lipid and synaptic signalling genes. 15,16 In humans, the C(-1019)G HTR1A promoter polymorphism associated with depression and suicide prevents regulation by Deaf1, altering brain-wide 5-HT1A receptor expression. 17,18 In Deaf1 knockout mice, despite similar alterations in 5-HT1A expression, adaptations in the signalling of 5-HT1A receptors across generations led to the development of a mild behavioural phenotype.…”

Section: J Psychiatry Neurosci 2017;42(1)mentioning

confidence: 99%

The adaptive brain in mental health: overcoming inherited risk factors

Albert

2017

JPN

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A primary function of the brain is to drive adaptation of the organism to its environment: learning, memory, attachment, fear, aggression, etc., are all manifestations of how the brain directs adaptation to the environment. One touch of a flame in youth is sufficient to engrain a learned behaviour that lasts a lifetime despite the memory of the specific event having long dissipated. To mediate these behaviours, the brain itself must adapt its transcriptional, structural and neurotransmission functions. This type of imprinted memory has been modelled in young Caenorhabditis elegans, where aversive memory is retained throughout the lifetime, while it is forgotten when adults are exposed.1 This persistent memory retention requires recruitment of new neurons that alone do not mediate memory retrieval, but that must be activated to permit memory retrieval via other neuronal circuits. Similarly, shocking mice in a given context generates a fear memory by recruiting a sparse subset of hippocampal neurons that can be reactivated to recruit the memory of the context. When these neurons are optogenetically inactivated, the fear memory is extinguished; when activated in a different context, this elicits an inappropriate fear response.2,3 Conversely, activating hippocampal cells that respond to a positive memory can reverse stress-induced depression-like behaviours. 4 Thus, one mechanism of brain adaptation involves cellular adaptation, with recruitment of new sets of neurons.Despite its potential for adaptation, the greatest risk factor for mental illness remains family history, 5 implicating genes, environment or both, and suggesting a limited capacity of the brain to adapt to these early and lifelong risk factors. The hypothesis that genetic makeup modifies the trajectory of adaptive behaviours underlies current efforts to identify specific genetic changes associated with mental illness. For example, genes associated with schizophrenia, such as NRG1, DISC1, or DTNBP1, undergo positive selection, suggesting that these genes drive a behavioural phenotype that may confer an evolutionary advantage in certain environments. 6 The question is whether potentially harmful inherited traits provoke homeostatic compensatory responses and whether these responses can be augmented through early interventions. Brain adaptation to inherited genetic and nongenetic risk in miceStudies in mouse models indicate that the brain can adapt to major genetic alterations, such as gene deletions or copy number variations, resulting in "normal" behavioural responses. Focusing on the serotonin (5-HT) system as an example, gene deletion of tryptophan hydroxylase2 (TPH2), the critical enzyme for synthesis of 5-HT in the brain, results in increased aggression and mildly reduced anxiety.7 Despite a greater than 90% loss of brain 5-HT levels, the TPH2 -/-mice show normal development and firing properties of 5-HT neurons, but show altered 5-HT innervation, 8 have compensatory upregulation of postsynaptic 5-HT1A and 5-HT1B receptors 9,10 and reduced 5-HT1A a...

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Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment

Cited by 42 publications

References 69 publications

Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment

Epigenetic Alterations Associated with War Trauma and Childhood Maltreatment

Interindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD

The adaptive brain in mental health: overcoming inherited risk factors

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