Effects of maternal separation and antidepressant drug on epigenetic regulation of the brain‐derived neurotrophic factor exon I promoter in the adult rat hippocampus

Park, Sung Woo; Seo, Mi Kyoung; Lee, Jung Goo; Hiền, Lê Thị Thu; Kim, Young Hoon

doi:10.1111/pcn.12609

Cited by 39 publications

(28 citation statements)

References 75 publications

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“…In our study, we observed that rats were subjected to MS every 3 h per day from PDN 1 to 21, and the immobility time increased when rats became adults [ 23 ]. We also showed that brain-derived neurotrophic factor (BDNF) and GR are involved in this mechanism, similar to previous studies [ 7 , 23 , 24 ].…”

Section: Discussionsupporting

confidence: 91%

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Effects of Early Life Stress on Epigenetic Changes of the Glucocorticoid Receptor 17 Promoter during Adulthood

Seo

Kim

Seog

et al. 2020

IJMS

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Growing evidence suggests that early life stress (ELS) has long-lasting effects on glucocorticoid receptor (GR) expression and behavior via epigenetic changes of the GR exon 17 promoter. However, it remains unclear whether ELS regulates histone modifications of the GR exon 17 promoter across the life span. We investigated the effects of maternal separation (MS) on histone acetylation and methylation of GR exon 17 promoter in the hippocampus, according to the age of adults. Depression-like behavior and epigenetic regulation of GR expression were examined at young and middle adulthood in mice subjected to MS from postnatal day 1 to 21. In the forced swimming test, young adult MS mice showed no effect on immobility time, but middle-aged MS mice significantly increased immobility time. Young adult and middle-aged MS mice showed decreased GR expression. Their two ages showed decreased histone acetylation with increased histone deacetylases (HDAC5) levels, decreased permissive methylation, and increased repressive methylation at the GR exon 17 promoter. The extent of changes in gene expression and histone modification in middle adulthood was greater than in young adulthood. These results indicate that MS in early life causes long-term negative effects on behavior via histone modification of the GR gene across the life span.

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Section: Discussionsupporting

confidence: 91%

“…The ChIP assay was used from the SimpleChIP ® Plus Enzymatic Chromatic IP kit (#9005, Cell Signaling, Beverly, MA, USA) according to the manufacturer’s instructions and as described previously [ 7 , 23 , 24 ]. Briefly, the DNA-protein of hippocampal tissue was crosslinked with 1.5% formaldehyde for 20 min at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Effects of Early Life Stress on Epigenetic Changes of the Glucocorticoid Receptor 17 Promoter during Adulthood

Seo

Kim

Seog

et al. 2020

IJMS

Self Cite

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“…MS stress occurring in the early phase of life can dramatically disrupt brain development and hence induce long-term changes, which may be the reason for the age-dependent effect of MS. Moreover, some studies report increased BDNF and decreased BDNF response to MS in the hippocampus and mPFC of rodents, respectively [68,69]; however, others do not [70,71]. The contradictory results may be related to the age of the animal as well as the duration of stress.…”

Section: Maternal Separationmentioning

confidence: 99%

The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF

Zhang

Wang

Sun

2020

IJMS

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Brain-derived neurotrophic factor (BDNF), a critical member of the neurotrophic family, plays an important role in multiple stress-related mental disorders. Although alterations in BDNF in multiple brain regions of individuals experiencing stress have been demonstrated in previous studies, it appears that a set of elements are involved in the complex regulation. In this review, we summarize the specific brain regions with altered BDNF expression during stress exposure. How various environmental factors, including both physical and psychological stress, affect the expression of BDNF in specific brain regions are further summarized. Moreover, epigenetic regulation of BDNF, including DNA methylation, histone modification, and noncoding RNA, in response to diverse types of stress, as well as sex differences in the sensitivity of BDNF to the stress response, is also summarized. Clarification of the underlying role of BDNF in the stress process will promote our understanding of the pathology of stress-linked mental disorders and provide a potent target for the future treatment of stress-related illness.

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“…It is also worth noting that recent studies based on animal models indicate positive effects of antidepressants which eliminate negative effects of epigenetic mechanisms [78,79]. However, as we mentioned earlier, the results of the research conducted so far are not clear.…”

Section: Oxytocin: Social Neuropeptide?mentioning

confidence: 89%

Epigenetic Mechanisms in the Neurodevelopmental Theory of Depression

Talarowska

2020

Depression Research and Treatment

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The genome (genes), epigenome, and environment work together from the earliest stages of human life to produce a phenotype of human health or disease. Epigenetic modifications, including among other things: DNA methylation, modifications of histones and chromatin structure, as well as functions of noncoding RNA, are coresponsible for specific patterns of gene expression. This refers also to mental disorders, including depressive disorders. Early childhood experiences accompanied by severe stressors (considered a risk factor for depression in adult life) are linked with changes in gene expression. They include genes involved in a response to stress (hypothalamic-pituitary-adrenal axis, HPA), associated with autonomic nervous system hyperactivity and with cortical, and subcortical processes of neuroplasticity and neurodegeneration. These are, among others: gene encoding glucocorticoid receptor, FK506 binding protein 5 gene (FKBP5), gene encoding arginine vasopressin and oestrogen receptor alpha, 5-hydroxy-tryptamine transporter gene (SLC6A4), and gene encoding brain-derived neurotrophic factor. How about personality? Can the experiences unique to every human being, the history of his or her development and gene-environment interactions, through epigenetic mechanisms, shape the features of our personality? Can we pass on these features to future generations? Hence, is the risk of depression inherent in our biological nature? Can we change our destiny?

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Effects of maternal separation and antidepressant drug on epigenetic regulation of the brain‐derived neurotrophic factor exon I promoter in the adult rat hippocampus

Abstract: These findings indicate that MS induced epigenetic changes at the BDNF exon I promoter and these changes were prevented by antidepressant drug treatment during adulthood.

Cited by 39 publications

References 75 publications

Effects of Early Life Stress on Epigenetic Changes of the Glucocorticoid Receptor 17 Promoter during Adulthood

Effects of Early Life Stress on Epigenetic Changes of the Glucocorticoid Receptor 17 Promoter during Adulthood

The Relationships Between Stress, Mental Disorders, and Epigenetic Regulation of BDNF

Epigenetic Mechanisms in the Neurodevelopmental Theory of Depression

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