Epigenomics
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Chronic pain arising from peripheral inflammation and tissue or nerve injury is a common clinical symptom. Although intensive research on the neurobiological mechanisms of chronic pain has been carried out during previous decades, this disorder is still poorly managed by current drugs such as opioids and nonsteroidal anti-inflammatory drugs. ⋯ Recent studies have shown that peripheral noxious stimulation changes DNA methylation and histone modifications and that these changes may be related to the induction of pain hypersensitivity under chronic pain conditions. This review summarizes the current knowledge and progress in epigenetic research in chronic pain and discusses the potential role of epigenetic modifications as therapeutic antinociceptive targets in this disorder.
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Review
The lasting legacy of social stress on the epigenome of the hypothalamic-pituitary-adrenal axis.
Social stress is a major factor contributing to early-life adversity that has taken on an epidemic scale. Early social stress leads to long-lasting changes in behavior, cognition, mood and neuroendocrine responses predisposing to or sheltering from stress-related diseases later in life. ⋯ Thereby, social stress-induced DNA memories mirror the complexity of the stress response and sex differences in brain epigenetics. Timely therapeutic interventions should aim to attenuate early social stress-derived DNA markings and their life-long consequences for mental health.
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Idiopathic pulmonary fibrosis (IPF) is a complex lung disease of unknown etiology. Development of IPF is influenced by both genetic and environmental factors. ⋯ This review will begin with an introduction to the disease, followed by brief summaries of studies of gene expression in IPF and epigenetic marks associated with exposures relevant to IPF. The majority of the discussion will focus on epigenetic studies conducted so far in IPF, the limitations, challenges nd future directions in this field.
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Epigenetic mechanisms have long been associated with the regulation of gene-expression changes accompanying normal neuronal development and cellular differentiation; however, until recently these mechanisms were believed to be statically quiet in the adult brain. Behavioral neuroscientists have now begun to investigate these epigenetic mechanisms as potential regulators of gene-transcription changes in the CNS subserving synaptic plasticity and long-term memory (LTM) formation. Experimental evidence from learning and memory animal models has demonstrated that active chromatin remodeling occurs in terminally differentiated postmitotic neurons, suggesting that these molecular processes are indeed intimately involved in several stages of LTM formation, including consolidation, reconsolidation and extinction. ⋯ The present article examines how such learning-induced epigenetic changes contribute to LTM formation and influence behavior. In particular, this article is a survey of the specific epigenetic mechanisms that have been demonstrated to regulate gene expression for both transcription factors and growth factors in the CNS, which are critical for LTM formation and storage, as well as how aberrant epigenetic processing can contribute to psychological states such as schizophrenia and drug addiction. Together, the findings highlighted in this article support a novel role for epigenetic mechanisms in the adult CNS serving as potential key molecular regulators of gene-transcription changes necessary for LTM formation and adult behavior.
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Classical genetic studies established a link between Type 1 diabetes, a common childhood autoimmune disease and genes that encode MHC antigens and several immune-related determinants. The mechanisms by which these genes contribute to the initiation and perpetuation of Type 1 diabetes remain enigmatic. ⋯ In this article the implications of these and other epigenetic mechanisms including ncRNA-mediated gene regulation in the abrogation of autoimmune diabetes are discussed. Concerted efforts to decipher the epigenetics of Type 1 diabetes may provide novel perspectives on autoimmune diabetogenesis.