Acute stress affects the global DNA methylation profile in rat brain: Modulation by physical exercise

Rodrigues, Gelson M.; Toffoli, Leandro Vaz; Manfredo, Marcelo H.; Oliveira, José Fernando de; Silva, Andrey S.; Raquel, Hiviny Ataides; Martins‐Pinge, Marli Cardoso; Moreira, Estefânia Gastaldello; Fernandes, Karen Barros Parron; Pelosi, Gislaine Garcia; Gomes, M.V.

doi:10.1016/j.bbr.2014.11.023

Cited by 60 publications

(40 citation statements)

References 33 publications

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“…Significant effects of MD were found in the dentate gyrus of hippocampus. Both groups that received methyl donors showed a significantly higher immunoreactivity (F (1,14) = 10.819, p<0.05; main effect of diet), indicating DNA hypermethylation as compared with the control group (Fig. 3b).…”

Section: -Methylcytosine Immunohistochemistrymentioning

confidence: 92%

“…The two-way ANOVA analysis indicated a marginal trend towards significance in the interaction between MS and the diet (F (1,14) = 4.191, p=0.068). Although post-hoc analysis can not be performed when ANOVA does not reach the level of significance (p<0.05), this result suggests a possible decrease in IR levels in the hippocampus of MS rats compared to controls that was reversed by MD (Fig.…”

Section: Hippocampal Expression Of Insulin Receptor By Western Blotmentioning

confidence: 96%

“…Mice lacking the gene MBD2 (methyl-CpG-binding domain protein 2) show neurobehavioural manifestations, while mice lacking DNMT1 only in the brain lose neurons and die after birth [8]. Acute stress has been demonstrated to affect both the global DNA methylation profile of the brain [14] and the methylation levels of genes implicated in the regulation of the hippocampal function, such as the glucocorticoid receptor [15]. Moreover, it has been described that early-life stress in rodents induces adult behavioural impairments [16] and leads to epigenetic alterations in different regions of the brain [17,18], affecting for example the methylation of the promoters of reelin [15] and corticotropin-releasing factor [19] in the adult rat brain.…”

Section: Introductionmentioning

confidence: 99%

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Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Paternain

Martišová

Campión

et al. 2016

Behavioural Brain Research

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Adverse early life events are associated with altered stress responsiveness and metabolic disturbances in the adult life. Dietary methyl donor supplementation could be able to reverse the negative effects of maternal separation by affecting DNA methylation in the brain. In this study, maternal separation during lactation reduced body weight gain in the female adult offspring without affecting food intake, and altered total and HDLcholesterol levels. Also, maternal separation induced a cognitive deficit as measured by NORT and an increase in the immobility time in the Porsolt forced swimming test, consistent with increased depression-like behaviour. An 18-week dietary supplementation with methyl donors (choline, betaine, folate and vitamin B12) from postnatal day 60 also reduced body weight without affecting food intake. Some of the deleterious effects induced by maternal separation, such as the abnormal levels of total and HDL-cholesterol, but especially the depression-like behaviour as measured by the Porsolt test, were reversed by methyl donor supplementation. Also, the administration of methyl donors increased total DNA methylation (measured by immunohistochemistry) and affected the expression of insulin receptor in the hippocampus of the adult offspring. However, no changes were observed in the DNA methylation status of insulin receptor and corticotropin-releasing hormone (CRH) promoter regions in the hypothalamus. In summary, methyl donor supplementation reversed some of the deleterious effects of an early life-induced model of depression in rats and altered the DNA methylation profile in the brain.

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Section: -Methylcytosine Immunohistochemistrymentioning

confidence: 92%

Section: Hippocampal Expression Of Insulin Receptor By Western Blotmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Paternain

Martišová

Campión

et al. 2016

Behavioural Brain Research

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“…The effectiveness of acute stress to induce epigenetic changes seems to not only depend on stressor frequency, but also on stressor dimension and severity, as 15 min of forced swimming and 30 min of predator exposure, but not 3 min of ether vapour exposure or 4 h of cold exposure, were found to increase H3 phosphorylation in the rat dentate gyrus (DG) (Bilang-Bleuel et al 2005). One hour of acute restraint stress also appeared to be sufficient to significantly decrease global DNA methylation levels in rat hippocampus, medial prefrontal cortex (mPFC), and periaqueductal grey (Rodrigues et al 2015). Possibly, stressors with a strong psychological component (such as restraint and predator exposure) might be more effective at inducing epigenetic changes than primarily physical stressors (such as cold and vapour exposure) (BilangBleuel et al 2005).…”

Section: Animal Studiesmentioning

confidence: 97%

Epigenetic programming of the neuroendocrine stress response by adult life stress

Dirven

Homberg

Kozicz

et al. 2017

Journal of Molecular Endocrinology

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The hypothalamic-pituitary-adrenal (HPA) axis is critically involved in the neuroendocrine regulation of stress adaptation, and the restoration of homeostasis following stress exposure. Dysregulation of this axis is associated with stress-related pathologies like major depressive disorder, post-traumatic stress disorder, panic disorder and chronic anxiety. It has long been understood that stress during early life can have a significant lasting influence on the development of the neuroendocrine system and its neural regulators, partially by modifying epigenetic regulation of gene expression, with implications for health and well-being in later life. Evidence is accumulating that epigenetic plasticity also extends to adulthood, proposing it as a mechanism by which psychological trauma later in life can long-lastingly affect HPA axis function, brain plasticity, neuronal function and behavioural adaptation to neuropsychological stress. Further corroborating this claim is the phenomenon that these epigenetic changes correlate with the behavioural consequences of trauma exposure. Thereby, epigenetic modifications provide a putative molecular mechanism by which the behavioural phenotype and transcriptional/translational potential of genes involved in HPA axis regulation can change drastically in response to environmental challenges, and appear an important target for treatment of stress-related disorders. However, improved insight is required to increase their therapeutic (drug) potential. Here, we provide an overview of the growing body of literature describing the epigenetic modulation of the (primarily neuroendocrine) stress response as a consequence of adult life stress and interpret the implications for, and the challenges involved in applying this knowledge to, the identification and treatment of stress-related psychiatric disorders.

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“…Decreases in global DNA methylation have been observed in the hippocampus, cortex, and periaqueductal gray of stressed (2007) animals ( Rodrigues et al 2015). Furthermore, in the hippocampus of stressed animals, the 3 ′ -UTR of the glucocorticoid receptor gene Nr3c1 was hyper-hydroxymethylated, a modification associated with increased transcription (Li et al 2015).…”

Section: The Neuroepigenetics Of Stressmentioning

confidence: 98%

The potential of epigenetics in stress-enhanced fear learning models of PTSD

et al. 2016

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Prolonged distress and dysregulated memory processes are the core features of post-traumatic stress disorder (PTSD) and represent the debilitating, persistent nature of the illness. However, the neurobiological mechanisms underlying the expression of these symptoms are challenging to study in human patients. Stress-enhanced fear learning (SEFL) paradigms, which encompass both stress and memory components in rodents, are emerging as valuable preclinical models of PTSD. Rodent models designed to study the long-term mechanisms of either stress or fear memory alone have identified a critical role for numerous epigenetic modifications to DNA and histone proteins. However, the epigenetic modifications underlying SEFL remain largely unknown. This review will provide a brief overview of the epigenetic modifications implicated in stress and fear memory independently, followed by a description of existing SEFL models and the few epigenetic mechanisms found to date to underlie SEFL. The results of the animal studies discussed here highlight neuroepigenetics as an essential area for future research in the context of PTSD through SEFL studies, because of its potential to identify novel candidates for neurotherapeutics targeting stress-induced pathogenic memories.Post-traumatic stress disorder (PTSD) is triggered by experiencing or witnessing a traumatic event and is characterized by pathogenic memory (e.g., recurrent, involuntary memories that trigger intense stress), avoidance of reminders, hyperarousal and reactivity, negative mood, cognitive alterations, and a persistence of symptoms for at least 1 mo. Although only a fraction of people exposed to trauma develop PTSD, a history of stress exposure prior to witnessing a traumatic event increases the risk (Breslau et al. 2014). Therefore, some animal models of PTSD use multidimensional stress and fear memory paradigms to model the disorder. In stress-enhanced fear learning (SEFL), a rodent is exposed to a stressor or combination of stressors prior to undergoing classical fear conditioning. Models that utilize SEFL closely reproduce many core symptoms of PTSD, including enhanced fear learning, generalized anxiety, heightened startle, and impaired extinction.

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Acute stress affects the global DNA methylation profile in rat brain: Modulation by physical exercise

Cited by 60 publications

References 33 publications

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Methyl donor supplementation in rats reverses the deleterious effect of maternal separation on depression-like behaviour

Epigenetic programming of the neuroendocrine stress response by adult life stress

The potential of epigenetics in stress-enhanced fear learning models of PTSD

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