scholarly journals The Molecular Basis of Depression: Implications of Sex-Related Differences in Epigenetic Regulation

2021 ◽  
Vol 14 ◽  
Author(s):  
Ayako Kawatake-Kuno ◽  
Toshiya Murai ◽  
Shusaku Uchida

Major depressive disorder (MDD) is a leading cause of disability worldwide. Although the etiology and pathophysiology of MDD remain poorly understood, aberrant neuroplasticity mediated by the epigenetic dysregulation of gene expression within the brain, which may occur due to genetic and environmental factors, may increase the risk of this disorder. Evidence has also been reported for sex-related differences in the pathophysiology of MDD, with female patients showing a greater severity of symptoms, higher degree of functional impairment, and more atypical depressive symptoms. Males and females also differ in their responsiveness to antidepressants. These clinical findings suggest that sex-dependent molecular and neural mechanisms may underlie the development of depression and the actions of antidepressant medications. This review discusses recent advances regarding the role of epigenetics in stress and depression. The first section presents a brief introduction of the basic mechanisms of epigenetic regulation, including histone modifications, DNA methylation, and non-coding RNAs. The second section reviews their contributions to neural plasticity, the risk of depression, and resilience against depression, with a particular focus on epigenetic modulators that have causal relationships with stress and depression in both clinical and animal studies. The third section highlights studies exploring sex-dependent epigenetic alterations associated with susceptibility to stress and depression. Finally, we discuss future directions to understand the etiology and pathophysiology of MDD, which would contribute to optimized and personalized therapy.

Author(s):  
Igor Ponomarev

Alcohol use disorder (AUD) is characterized by clinically significant impairments in health and social function. Epigenetic mechanisms of gene regulation may provide an attractive explanation for how early life exposures to alcohol contribute to the development of AUD and exert lifelong effects on the brain. This chapter provides a critical discussion of the role of epigenetic mechanisms in AUD etiology and the potential of epigenetic research to improve diagnosis, evaluate risks for alcohol-induced pathologies, and promote development of novel therapies for the prevention and treatment of AUD. Challenges of the current epigenetic approaches and future directions are also discussed.


2021 ◽  
Author(s):  
Jared S. Katzeff ◽  
Woojin Scott Kim

Abstract ATP-binding cassette (ABC) transporters are one of the largest groups of transporter families in humans. ABC transporters mediate the translocation of a diverse range of substrates across cellular membranes, including amino acids, nucleosides, lipids, sugars and xenobiotics. Neurodegenerative diseases are a group of brain diseases that detrimentally affect neurons and other brain cells and are usually associated with deposits of pathogenic proteins in the brain. Major neurodegenerative diseases include Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. ABC transporters are highly expressed in the brain and have been implicated in a number of pathological processes underlying neurodegenerative diseases. This review outlines the current understanding of the role of ABC transporters in neurodegenerative diseases, focusing on some of the most important pathways, and also suggests future directions for research in this field.


Author(s):  
Priyadarshni Patel ◽  
Jeganathan Ramesh Babu ◽  
Xu Wang ◽  
Thangiah Geetha

Obesity is caused by a combination of hereditary and environmental factors. Despite extensive study, contemporary through diet, exercise, education, surgery, and pharmacological treatments, no effective long-term solution has been found to this epidemic. Over the last decade, there has been a tremendous advancement in understanding the science of epigenetics, as well as a rise in public interest in learning more about the influence of diet and lifestyle choices on the health of an individual. Without affecting the underlying DNA sequence, epigenetic alterations impact gene expression. Previous animal studies have shown a link between the type of diet and expression or suppression of obesity genes, but there are very few human studies that demonstrate the relationship between dietary intake and obesity gene expression. This review highlights the effects of carbohydrates, lipids, and protein intake from the diet on obesity-related genes.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Annamaria Srancikova ◽  
Zuzana Bacova ◽  
Jan Bakos

Abstract Epigenetic mechanisms greatly affect the developing brain, as well as the maturation of synapses with pervasive, long-lasting consequences on behavior in adults. Substantial evidence exists that implicates dysregulation of epigenetic mechanisms in the etiology of neurodevelopmental disorders. Therefore, this review explains the role of enzymes involved in DNA methylation and demethylation in neurodevelopment by emphasizing changes of synaptic genes and proteins. Epigenetic causes of sex-dependent differences in the brain are analyzed in conjunction with the pathophysiology of autism spectrum disorders. Special attention is devoted to the epigenetic regulation of the melanoma-associated antigen-like gene 2 (MAGEL2) found in Prader-Willi syndrome, which is known to be accompanied by autistic symptoms.


Epigenomics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Andrew M Shafik ◽  
Emily G Allen ◽  
Peng Jin

N6-methyladenosine (m6A) is a dynamic RNA modification that regulates various aspects of RNA metabolism and has been implicated in many biological processes and transitions. m6A is highly abundant in the brain; however, only recently has the role of m6A in brain development been a focus. The machinery that controls m6A is critically important for proper neurodevelopment, and the precise mechanisms by which m6A regulates these processes are starting to emerge. However, the role of m6A in neurodegenerative and neuropsychiatric diseases still requires much elucidation. This review discusses and summarizes the current body of knowledge surrounding the function of the m6A modification in regulating normal brain development, neurodegenerative diseases and outlines possible future directions.


2020 ◽  
Vol 24 (4) ◽  
pp. 196-203
Author(s):  
Jang Mee Kim ◽  
Ji Yeon Lee

Intrauterine inflammation is defined as the inflammation of the chorion, amnion, and placenta. Untreated inflammation increases the risk of fetal inflammatory response syndrome, which may result in multiorgan diseases involving the brain, cardiovascular system, lung, eye, and intestine. Therefore, controlling inflammation is critical in pregnant women to reduce the risk of diseases. However, there are no safe and effective anti-inflammatory drugs for administration during pregnancy. Although the primary function of melatonin is to control circadian rhythms, it has protective effects against cellular insults occurring from hypoxia, oxidative stress, and inflammation. While animal studies support the effective and safe role of melatonin in improving pregnancy-related morbidities, it leaves plenty of opportunities for clinical studies investigating its anti-inflammatory, antioxidant, and protective effects against insults induced by intrauterine inflammation. Therefore, it will be worthwhile to investigate antenatal supplementation of melatonin in pregnant women with intrauterine inflammation to reduce the incidence of associated comorbidities.


Author(s):  
Bryan T. Denny ◽  
Kevin N. Ochsner

This chapter takes a social cognitive affective neuroscience approach to describe the processes and systems to give rise to emotion and the volitional control of emotion. It provides a detailed description of the processes that underlie the regulation of emotion. It introduces and synthesizes the brain structures involved in emotion processing and regulation. There is a particular focus on the role of the ventrolateral, dorsolateral and dorsomedial prefrtonal cortex, amgydala, ventral striatum and insula, and on cognitive strategies such as reappraisal. It provides a critical framework for understanding the underlying behavioral and neural basis for the affect dysregulation observed across personality disorders, and summarizes future directions for this area of investigation.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Yongxin Li ◽  
Feiyan Chen ◽  
Wenhua Huang

The human brain has an enormous capacity to adapt to a broad variety of environmental demands. Previous studies in the field of abacus training have shown that this training can induce specific changes in the brain. However, the neural mechanism underlying these changes remains elusive. Here, we reviewed the behavioral and imaging findings of comparisons between abacus experts and average control subjects and focused on changes in activation patterns and changes in brain structure. Finally, we noted the limitations and the future directions of this field. We concluded that although current studies have provided us with information about the mechanisms of abacus training, more research on abacus training is needed to understand its neural impact.


Symmetry ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 1257
Author(s):  
Marco Dadda ◽  
Veronica Vendramin ◽  
Christian Agrillo

The role of genetic and environmental factors in modulating the development of brain lateralization is far from being fully understood, and the presence of individual differences in several lateralized functions is still an open question. In goldbelly topminnows, the genetic basis of asymmetrical functions in the brain has been studied, and recently it has been found that light stimulation influences the expression of lateralization of newborns. Here, we investigated whether prenatal exposure to predators affects the development of lateralization in 10-day-old topminnows born from females exposed to a real or to a simulated predator during pregnancy. Offspring from females exposed to a real predator were lateralized in both visual and motor tests, whereas fish from females exposed to a simulated predator were not and did not differ from controls. Prenatal exposure to a real predator might promote the alignment of lateralization in the same direction in different individuals.


2020 ◽  
Vol 133 (17) ◽  
pp. jcs231423
Author(s):  
Wim Annaert ◽  
Christoph Kaether

ABSTRACTThe quote “bring it back, bring it back, don't take it away from me” from Queen's Love of my life describes the function of the sorting receptor RER1, a 23 kDa protein with four transmembrane domains (TMDs) that localizes to the intermediate compartment and the cis-Golgi. From there it returns escaped proteins that are not supposed to leave the endoplasmic reticulum (ER) back to it. Unique about RER1 is its ability to recognize its ligands through binding motifs in TMDs. Among its substrates are ER-resident proteins, as well as unassembled subunits of multimeric complexes that are retrieved back into the ER, this way guarding the full assembly of their respective complexes. The basic mechanisms for RER1-dependent retrieval have been already elucidated some years ago in yeast. More recently, several important cargoes of RER1 have been described in mammalian cells, and the in vivo role of RER1 is being unveiled by using mouse models. In this Review, we give an overview of the cell biology of RER1 in different models, discuss its controversial role in the brain and provide an outlook on future directions for RER1 research.


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