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Progress in Molecular Biology and Translational Science

Stephan Claes
Life does not start at birth but at conception. What a person experiences during the first 9 months of life in the intrauterine environment will have lasting effects on health and disease later in life. Psychological stress in pregnant women has a number of potential negative consequences for the physical and psychological function of their children. The mechanisms driving this association are, among others, epigenetic modifications at specific loci in the infant DNA. In the chapter, the relevant animal and human studies underlying these assumptions are reviewed, and it is argued that they are convincingly supported by the evidence...
2018: Progress in Molecular Biology and Translational Science
Roy Lardenoije, Ehsan Pishva, Katie Lunnon, Daniel L van den Hove
Neurodegenerative diseases are complex, progressive disorders and affect millions of people worldwide, contributing significantly to the global burden of disease. In recent years, research has begun to investigate epigenetic mechanisms for a potential role in disease etiology. In this chapter, we describe the current state of play for epigenetic research into neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and Huntington's disease. We focus on the recent evidence for a potential role of DNA modifications, histone modifications and non-coding RNA in the etiology of these disorders...
2018: Progress in Molecular Biology and Translational Science
Chiara Renzi, Nadine Provencal, Katherine C Bassil, Kathinka Evers, Ulrik Kihlbom, Elizabeth J Radford, Ilona Koupil, Bertram Mueller-Myhsok, Mats G Hansson, Bart P F Rutten
The development of mental disorders constitutes a complex phenomenon driven by unique social, psychological and biological factors such as genetics and epigenetics, throughout an individual's life course. Both environmental and genetic factors have an impact on mental health phenotypes and act simultaneously to induce changes in brain and behavior. Here, we describe and critically evaluate the current literature on gene-environment interactions and epigenetics on mental health by highlighting recent human and animal studies...
2018: Progress in Molecular Biology and Translational Science
Elizabeth J Radford
The astonishing array of cellular phenotypes required to make a complex organism such as a human is generated from an identical genetic sequence in the nucleus of each cell. The central nervous system is a highly ordered, complex system composed of multiple neuronal and glial cell types. Both neurons and glia are derived from neural stem/precursor cells (NPCs) in a temporally and spatially patterned process of cellular division and differentiation, migration, maturation and the establishment of neuronal connectivity...
2018: Progress in Molecular Biology and Translational Science
Ali Jawaid, Martin Roszkowski, Isabelle M Mansuy
Traumatic stress is a type of environmental experience that can modify behavior, cognition and physiological functions such as metabolism, in mammals. Many of the effects of traumatic stress can be transmitted to subsequent generations even when individuals from these generations are not exposed to any traumatic stressor. This book chapter discusses the concept of epigenetic/non-genomic inheritance of such traits involving the germline in mammals. It includes a comprehensive review of animal and human studies on inter- and transgenerational inheritance of the effects of traumatic stress, some of the epigenetic changes in the germline currently known to be associated with traumatic stress, and possible mechanisms for their induction and maintenance during development and adulthood...
2018: Progress in Molecular Biology and Translational Science
Laura M Fiori, Rixing Lin, Chelsey Ju, Raoul Belzeaux, Gustavo Turecki
Major depressive disorder is a chronic and debilitating illness. It is most commonly treated with antidepressant drugs, however, as the majority of patients do not respond on their first trial or following several adequate trials, there is great interest in identifying biological factors that may help select the most appropriate treatment for each patient and in understanding biological processes that mediate treatment response. Epigenetic factors, such as non-coding RNAs (ncRNAs), hold potential as biomarkers of antidepressant response...
2018: Progress in Molecular Biology and Translational Science
Grace S Kim, Alicia K Smith, Caroline M Nievergelt, Monica Uddin
While diagnosis of PTSD is based on behavioral symptom clusters that are most directly associated with brain function, epigenetic studies of PTSD in humans to date have been limited to peripheral tissues. Animal models of PTSD have been key for understanding the epigenetic alterations in the brain most directly relevant to endophenotypes of PTSD, in particular those pertaining to fear memory and stress response. This chapter provides an overview of neuroepigenetic studies based on animal models of PTSD, with an emphasis on the effect of stress on fear memory...
2018: Progress in Molecular Biology and Translational Science
Giovanna Punzi, Rahul Bharadwaj, Gianluca Ursini
Schizophrenia is a complex disorder of the brain, where genetic variants explain only a portion of risk. Neuroepigenetic mechanisms may explain the remaining share of risk, as well as the transition from susceptibility to the actual disease. Here, we discuss the most recent findings in the field of brain epigenetics applied to the study of schizophrenia. Methylome studies have found several candidates exhibiting methylation modifications in association with the disorder, but genes affected do not always overlap...
2018: Progress in Molecular Biology and Translational Science
Mathilde Règue-Guyon, Laurence Lanfumey, Raymond Mongeau
This review examines the epigenetic of neurotrophin signaling in anxiety, affective disorders and related symptoms associated with drug addiction, in particular alcoholism. It is first important to understand the epigenetics of aversion memories, as they are so central to anxiety and affective disorders symptomology. The crucial role of neurotrophins in memory formation, in particular the brain-derived nerve growth factor (BDNF), is explored at the physiological and behavioral levels. Numerous studies describe how various epigenetic phenomena, mainly histone acetylation, histone methylation, DNA methylation, but also other less known epigenetic phenomena such as histone poly[ADP]-ribosylation and 5-HT2C receptor pre-mRNA editing, exert significant regulatory roles in aversion memory and fear extinction memory formation...
2018: Progress in Molecular Biology and Translational Science
Clara Snijders, Katherine C Bassil, Laurence de Nijs
Over the last years, interest in epigenetic mechanisms has strongly increased in the field of neuroscience. Neuroepigenetics has intensely evolved and now refers to the assessment of a variety of epigenetic marks which can be found across several regions of the healthy or diseased brain. These marks include DNA (hydroxy)methylation, a large diversity of post-translational histone modifications and an increasing number of non-coding RNAs. The present chapter aims to concisely summarize the techniques used to study these mechanisms in the brain and provides an overview of their current challenges along with future perspectives that will allow the field to move forward...
2018: Progress in Molecular Biology and Translational Science
Ramona A J Zwamborn, Clara Snijders, Ning An, Alix Thomson, Bart P F Rutten, Laurence de Nijs
The Wnt signaling pathway has been recognized as an important pathway, extending its function throughout the lifespan. Evidence suggests that dysfunctional Wnt signaling in the adult brain leads to aberrant neurogenesis, synaptogenesis, modulation of mature synapses and neurotransmitter release in the hippocampus. Due to the involvement of Wnt proteins in hippocampal functioning, altered Wnt signaling has been suggested to be an important factor in the pathophysiology of mood disorders. Interestingly, the effects of mood-stabilizing drugs are believed to work through interactions with Wnt molecules, and epigenetic mechanisms have been shown to interact with components of the Wnt pathway and impact mechanisms such as synaptic plasticity...
2018: Progress in Molecular Biology and Translational Science
Alec Dick, Nadine Provencal
Dynamic adaptation to stressful life events requires the co-ordinated action of the central stress response, which is mediated by the hypothalamic-pituitary-adrenal (HPA) axis, to restore and maintain homeostasis. Excessive exposure to stress or traumatic life events, such as childhood maltreatment, has been linked to HPA axis dysfunction increasing the risk of developing stress-related psychopathologies such as major depressive disorder and post-traumatic-stress-disorder. Mounting evidence supports the notion that stressors throughout pre- and postnatal development as well as adulthood can induce neuroepigenetic regulation of gene expression within key nodes of the brain, which may in part mediate such HPA axis dysfunction...
2018: Progress in Molecular Biology and Translational Science
Bart P F Rutten
Epigenetics refers to environmentally sensitive modifications to DNA and chromatin that regulate gene transcription without altering the genetic sequence itself. Because of the brain's central role in a person's adaptation to dynamic changes in the environment, the field of epigenetic research is particularly pertinent for the neurosciences and mental health and illness. "Neuroepigenetics" refers to the field of epigenetics, as applied to research of the nervous system and related functional abilities...
2018: Progress in Molecular Biology and Translational Science
Elad Lax, Moshe Szyf
Drug addiction is a devastating health problem that is a very heavy burden on the individual affected and the society in general. Recent research defines addiction as a neurobehavioral disorder. Underpinning biological mechanisms of drug addiction are abnormal neuronal and brain activity following acute and repeated drug exposure. Abnormal gene expression is found in reward and decision-making brain regions of addicts and in animal models and is possibly responsible for changes in brain function. DNA methylation is an epigenetic modification that regulates gene expression...
2018: Progress in Molecular Biology and Translational Science
Rochelle L Coulson, Janine M LaSalle
DNA sequence information alone cannot account for the immense variability between chromosomal alleles within diverse cell types in the brain, whether these differences are observed across time, cell type, or parental origin. The complex control and maintenance of gene expression and modulation are regulated by a multitude of molecular and cellular mechanisms that layer on top of the genetic code. The integration of genetic and environmental signals required for regulating brain development and function is achieved in part by a dynamic epigenetic landscape that includes DNA methylation, histone modifications, and noncoding RNAs...
2018: Progress in Molecular Biology and Translational Science
Catherine J Peña, Eric J Nestler
Depression is a prevalent and complex psychiatric syndrome. Epigenetic mechanisms bridge the genetic and environmental factors that contribute to the pathophysiology of depression. A surge of research over the last decade has identified changes in DNA methylation, histone modifications, histone organization, and noncoding RNAs associated with depression and stress-induced depression-like behavior in animal models. We focus here on associations of epigenetic factors concurrent with depression and depression-like behavior, although risk for depression and some of the associated epigenetic changes are known to have developmental origins...
2018: Progress in Molecular Biology and Translational Science
Sarah Barnett Burns, Daniel Almeida, Gustavo Turecki
Adverse experiences during sensitive postnatal developmental periods can disrupt the calibration of fundamental systems and increase the risk of a wide range of adult disease states, including psychiatric illnesses. Accumulating evidence suggests that epigenetic modifications involving DNA methylation, posttranslational histone modifications, and noncoding RNAs may be a key mediating factor in this disruption. Accumulating evidence from both animal models and human studies suggests that early life adversity alters the epigenome at multiple loci across the genome, but that the specific alterations, and the associated transcriptomic and psychiatric outcomes may be dependent on multiple individual factors...
2018: Progress in Molecular Biology and Translational Science
Amanda H Mahnke, Nihal A Salem, Alexander M Tseng, Dae D Chung, Rajesh C Miranda
Early developmental exposure to ethanol, a known teratogen, can result in a range of neurodevelopmental disorders, collectively referred to as Fetal Alcohol Spectrum Disorders (FASDs). Changes in the environment, including exposure to teratogens, can result in long term alterations to the epigenetic landscape of a cell, thereby altering gene expression. Noncoding RNAs (ncRNAs) can affect transcription and translation of networks of genes. ncRNAs are dynamically expressed during development and have been identified as a target of alcohol...
2018: Progress in Molecular Biology and Translational Science
Nagalakshmi B, Sneha Sagarkar, Amul J Sakharkar
Of all types of injuries, traumatic brain injuries (TBIs) are most likely to result in death or permanent physical or mental disabilities. With the increased frequency of military operations, terror attacks, sports activities, and road mishaps, TBIs are increasingly becoming a serious public health concern. Patients who meet with moderate-to-severe TBI suffer from a constellation of cognitive deficits and phenotypes due to diffuse axonal injury. On the contrary, minimal TBI precipitates in long-term behavioral complications commonly referred to as post-traumatic stress disorders, which consist of depression, anxiety, hallucinations, and so on...
2018: Progress in Molecular Biology and Translational Science
Bhaskar Roy, Yogesh Dwivedi
Stressful life incidents often cause a predisposition for developing mental disorders such as major depressive disorder (MDD). Impaired neurocognitive and neuro-vegetative functions of the central nervous system are the hallmarks of this mental illness. Blunted responses from emotionally salient regions of the brain including cortex, hippocampus, and amygdala have been associated with MDD-related behavioral changes. Moreover, improper signal processing and neuronal atrophy were held responsible for the overall dysfunctionality of these vulnerable regions in the MDD brain...
2018: Progress in Molecular Biology and Translational Science
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