scholarly journals Epigenetic Regulation of Gene Expression in Physiological and Pathological Brain Processes

2011 ◽  
Vol 91 (2) ◽  
pp. 603-649 ◽  
Author(s):  
Johannes Gräff ◽  
Dohoon Kim ◽  
Matthew M. Dobbin ◽  
Li-Huei Tsai
Keyword(s):  
Regulation Of Gene Expression ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanisms ◽  
Brain Functions ◽  
Epigenetic Machinery ◽  
Complex Functions ◽  
Cell Type Specific ◽  
Neuronal Functions ◽  
The Brain ◽  
Unique Potential

Over the past decade, it has become increasingly obvious that epigenetic mechanisms are an integral part of a multitude of brain functions that range from the development of the nervous system over basic neuronal functions to higher order cognitive processes. At the same time, a substantial body of evidence has surfaced indicating that several neurodevelopmental, neurodegenerative, and neuropsychiatric disorders are in part caused by aberrant epigenetic modifications. Because of their inherent plasticity, such pathological epigenetic modifications are readily amenable to pharmacological interventions and have thus raised justified hopes that the epigenetic machinery provides a powerful new platform for therapeutic approaches against these diseases. In this review, we give a detailed overview of the implication of epigenetic mechanisms in both physiological and pathological brain processes and summarize the state-of-the-art of “epigenetic medicine” where applicable. Despite, or because of, these new and exciting findings, it is becoming apparent that the epigenetic machinery in the brain is highly complex and intertwined, which underscores the need for more refined studies to disentangle brain-region and cell-type specific epigenetic codes in a given environmental condition. Clearly, the brain contains an epigenetic “hotspot” with a unique potential to not only better understand its most complex functions, but also to treat its most vicious diseases.

scholarly journals A whole-brain connectivity map of mouse insular cortex

2020 ◽  
Author(s):  
Daniel A. Gehrlach ◽  
Thomas N. Gaitanos ◽  
Alexandra S. Klein ◽  
Caroline Weiand ◽  
Alexandru A. Hennrich ◽  
...  
Keyword(s):  
Brain Connectivity ◽  
Insular Cortex ◽  
Structural Basis ◽  
Subcortical Structures ◽  
Whole Brain ◽  
Brain Functions ◽  
Complex Functions ◽  
Cell Type Specific ◽  
Cortical Regions ◽  
The Brain

AbstractThe insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. We employed cell-type specific monosynaptic rabies virus tracings to characterize afferent connections onto either excitatory or inhibitory IC neurons, and adeno-associated viral tracings to label excitatory efferent axons. While the connectivity between the IC and other cortical regions was highly reciprocal, the IC connectivity with subcortical structures was often unidirectional, revealing prominent top-down and bottom-up pathways. The posterior and medial IC exhibited resembling connectivity patterns, while the anterior IC connectivity was distinct, suggesting two major functional compartments. Our results provide insights into the anatomical architecture of the mouse IC and thus a structural basis to guide investigations into its complex functions.

scholarly journals A whole-brain connectivity map of mouse insular cortex

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Daniel A Gehrlach ◽  
Caroline Weiand ◽  
Thomas N Gaitanos ◽  
Eunjae Cho ◽  
Alexandra S Klein ◽  
...  
Keyword(s):  
Brain Connectivity ◽  
Insular Cortex ◽  
Structural Basis ◽  
Subcortical Structures ◽  
Whole Brain ◽  
Brain Functions ◽  
Complex Functions ◽  
Cell Type Specific ◽  
Cortical Regions ◽  
The Brain

The insular cortex (IC) plays key roles in emotional and regulatory brain functions and is affected across psychiatric diseases. However, the brain-wide connections of the mouse IC have not been comprehensively mapped. Here, we traced the whole-brain inputs and outputs of the mouse IC across its rostro-caudal extent. We employed cell-type-specific monosynaptic rabies virus tracings to characterize afferent connections onto either excitatory or inhibitory IC neurons, and adeno-associated viral tracings to label excitatory efferent axons. While the connectivity between the IC and other cortical regions was highly bidirectional, the IC connectivity with subcortical structures was often unidirectional, revealing prominent cortical-to-subcortical or subcortical-to-cortical pathways. The posterior and medial IC exhibited resembling connectivity patterns, while the anterior IC connectivity was distinct, suggesting two major functional compartments. Our results provide insights into the anatomical architecture of the mouse IC and thus a structural basis to guide investigations into its complex functions.

scholarly journals Epigenetic mechanisms in sexual differentiation of the brain and behaviour

2016 ◽  
Vol 371 (1688) ◽  
pp. 20150114 ◽  
Author(s):  
Nancy G. Forger
Keyword(s):  
Gene Expression ◽  
Sex Differences ◽  
Sexual Differentiation ◽  
Wide Distribution ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Genome Wide ◽  
The Brain

Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour.

Epigenetics

2013 ◽  
Author(s):  
Steffen Gay ◽  
Michel Neidhart
Keyword(s):  
Lupus Erythematosus ◽  
Regulation Of Gene Expression ◽  
Pathological Process ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanisms ◽  
Epigenetic Changes ◽  
Therapeutic Concept ◽  
Methyl Donors ◽  
Chromatin Folding ◽  
Eukaryotic Organisms

In higher eukaryotic organisms epigenetic modifications are crucial for proper chromatin folding and thereby proper regulation of gene expression. Epigenetics include DNA methylation, histone modifications, and microRNAs. First described in tumors, the involvement of aberrant epigenetic modifications has been reported also in other diseases, i.e. metabolic, psychiatric, inflammatory, and autoimmune. Deregulation of epigenetic mechanisms occurred in patients with rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Many questions remain: e.g. what is the cause of these epigenetic changes and how can we interfere in the pathological process? Here we discuss whether supplementation with methyl donors could represent a novel therapeutic concept for such diseases.

Epigenetics

2013 ◽  
pp. 296-306
Author(s):  
Steffen Gay ◽  
Michel Neidhart
Keyword(s):  
Lupus Erythematosus ◽  
Regulation Of Gene Expression ◽  
Pathological Process ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanisms ◽  
Therapeutic Concept ◽  
Methyl Donors ◽  
Chromatin Folding ◽  
Eukaryotic Organisms ◽  
Novel Therapeutic

In higher eukaryotic organisms epigenetic modifications are crucial for proper chromatin folding and thereby proper regulation of gene expression. Epigenetics include DNA methylation, histone modifications, and microRNAs. First described in tumors, the involvement of aberrant epigenetic modifications has been reported also in other diseases, i.e. metabolic, psychiatric, inflammatory, and autoimmune. Deregulation of epigenetic mechanisms occurred in patients with rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Many questions remain: e.g. what is the cause of these epigenetic changes and how can we interfere in the pathological process? Here we discuss whether supplementation with methyl donors could represent a novel therapeutic concept for such diseases.

scholarly journals Transposon-mediated, cell type-specific transcription factor recording in the mouse brain

2019 ◽  
Author(s):  
Alexander J. Cammack ◽  
Arnav Moudgil ◽  
Tomas Lagunas ◽  
Michael J. Vasek ◽  
Mark Shabsovich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Mouse Tissue ◽  
Specific Cell ◽  
Cell Type ◽  
Cell Fate Decisions ◽  
Cell Type Specific ◽  
The Brain

AbstractTranscription factors (TFs) play a central role in the regulation of gene expression, controlling everything from cell fate decisions to activity dependent gene expression. However, widely-used methods for TF profiling in vivo (e.g. ChIP-seq) yield only an aggregated picture of TF binding across all cell types present within the harvested tissue; thus, it is challenging or impossible to determine how the same TF might bind different portions of the genome in different cell types, or even to identify its binding events at all in rare cell types in a complex tissue such as the brain. Here we present a versatile methodology, FLEX Calling Cards, for the mapping of TF occupancy in specific cell types from heterogenous tissues. In this method, the TF of interest is fused to a hyperactive piggyBac transposase (hypPB), and this bipartite gene is delivered, along with donor transposons, to mouse tissue via a Cre-dependent adeno-associated virus (AAV). The fusion protein is expressed in Cre-expressing cells where it inserts transposon “Calling Cards” near to TF binding sites. These transposons permanently mark TF binding events and can be mapped using high-throughput sequencing. Alternatively, unfused hypPB interacts with and records the binding of the super enhancer (SE)-associated bromodomain protein, Brd4. To demonstrate the FLEX Calling Card method, we first show that donor transposon and transposase constructs can be efficiently delivered to the postnatal day 1 (P1) mouse brain with AAV and that insertion profiles report TF occupancy. Then, using a Cre-dependent hypPB virus, we show utility of this tool in defining cell type-specific TF profiles in multiple cell types of the brain. This approach will enable important cell type-specific studies of TF-mediated gene regulation in the brain and will provide valuable insights into brain development, homeostasis, and disease.

scholarly journals Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer’s Disease

2021 ◽  
Vol 22 (22) ◽  
pp. 12280
Author(s):  
Sabyasachi Maity ◽  
Kayla Farrell ◽  
Shaghayegh Navabpour ◽  
Sareesh Naduvil Narayanan ◽  
Timothy J. Jarome
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Memory Loss ◽  
Memory Formation ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanisms ◽  
Post Translational Modifications ◽  
Memory Decline ◽  
The Brain

Epigenetic mechanisms, which include DNA methylation, a variety of post-translational modifications of histone proteins (acetylation, phosphorylation, methylation, ubiquitination, sumoylation, serotonylation, dopaminylation), chromatin remodeling enzymes, and long non-coding RNAs, are robust regulators of activity-dependent changes in gene transcription. In the brain, many of these epigenetic modifications have been widely implicated in synaptic plasticity and memory formation. Dysregulation of epigenetic mechanisms has been reported in the aged brain and is associated with or contributes to memory decline across the lifespan. Furthermore, alterations in the epigenome have been reported in neurodegenerative disorders, including Alzheimer’s disease. Here, we review the diverse types of epigenetic modifications and their role in activity- and learning-dependent synaptic plasticity. We then discuss how these mechanisms become dysregulated across the lifespan and contribute to memory loss with age and in Alzheimer’s disease. Collectively, the evidence reviewed here strongly supports a role for diverse epigenetic mechanisms in memory formation, aging, and neurodegeneration in the brain.

scholarly journals Maternal Obesity, Maternal Overnutrition and Fetal Programming: Effects of Epigenetic Mechanisms on the Development of Metabolic Disorders

2019 ◽  
Vol 20 (6) ◽  
pp. 419-427 ◽  
Author(s):  
Ezgi Şanlı ◽  
Seray Kabaran
Keyword(s):  
Fetal Programming ◽  
Metabolic Disorders ◽  
Maternal Obesity ◽  
Metabolic Diseases ◽  
Regulation Of Gene Expression ◽  
Epigenetic Modifications ◽  
Epigenetic Mechanisms ◽  
Maternal Overnutrition ◽  
The Impact

Background: Maternal obesity and maternal overnutrition, can lead to epigenetic alterations during pregnancy and these alterations can influence fetal and neonatal phenotype which increase the risk of metabolic disorders in later stages of life. Objective: The effects of maternal obesity on fetal programming and potential mechanisms of maternal epigenetic regulation of gene expression which have persistent effects on fetal health and development were investigated. Method: Review of the literature was carried out in order to discuss the effects of maternal obesity and epigenetic mechanisms in fetal programming of metabolic disorders. All abstracts and full-text articles were examined and the most relevant articles were included in this review. Results: Maternal obesity and maternal overnutrition during fetal period has important overall effects on long-term health. Maternal metabolic alterations during early stages of fetal development can lead to permanent changes in organ structures, cell numbers and metabolism. Epigenetic modifications (DNA methylation, histone modifications, microRNAs) play an important role in disease susceptibility in the later stages of human life. Maternal nutrition alter expression of hypothalamic genes which can increase fetal and neonatal energy intake. Epigenetic modifications may affect the increasing rate of obesity and other metabolic disorders worldwide since the impact of these changes can be passed through generations. Conclusion: Weight management before and during pregnancy, together with healthy nutritional intakes may improve the maternal metabolic environment, which can reduce the risks of fetal programming of metabolic diseases. Further evidence from long-term follow-up studies are needed in order to determine the role of maternal obesity on epigenetic mechanisms.

TEORI KECERDASAN, PENDIDIKAN ANAK, DAN KOMUNIKASI DALAM KELUARGA

1970 ◽  
Vol 6 (1) ◽  
Author(s):  
Muskinul Fuad
Keyword(s):  
Multiple Intelligences ◽  
Educational Activity ◽  
Howard Gardner ◽  
Human Beings ◽  
Brain Functions ◽  
Starting Point ◽  
The Family ◽  
Education Today ◽  
The Brain ◽  
Spatial Logics

The education system in Indonesia emphasize on academic intelligence, whichincludes only two or three aspects, more than on the other aspects of intelligence. For thatreason, many children who are not good at academic intelligence, but have good potentials inother aspects of intelligence, do not develop optimally. They are often considered and labeledas "stupid children" by the existing system. This phenomenon is on the contrary to the theoryof multiple intelligences proposed by Howard Gardner, who argues that intelligence is theability to solve various problems in life and produce products or services that are useful invarious aspects of life.Human intelligence is a combination of various general and specific abilities. Thistheory is different from the concept of IQ (intelligence quotient) that involves only languageskills, mathematical, and spatial logics. According to Gardner, there are nine aspects ofintelligence and its potential indicators to be developed by each child born without a braindefect. What Gardner suggested can be considered as a starting point to a perspective thatevery child has a unique individual intelligence. Parents have to treat and educate theirchildren proportionally and equitably. This treatment will lead to a pattern of education that isfriendly to the brain and to the plurality of children’s potential.More than the above points, the notion that multiple intelligences do not just comefrom the brain needs to be followed. Humans actually have different immaterial (spiritual)aspects that do not refer to brain functions. The belief in spiritual aspects and its potentialsmeans that human beings have various capacities and they differ from physical capacities.This is what needs to be addressed from the perspective of education today. The philosophyand perspective on education of the educators, education stakeholders, and especially parents,are the first major issue to be addressed. With this step, every educational activity andcommunication within the family is expected to develop every aspect of children'sintelligence, especially the spiritual intelligence.

Alcohol Use Disorder

2018 ◽  
Author(s):  
Igor Ponomarev
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Critical Discussion ◽  
Epigenetic Mechanisms ◽  
Future Directions ◽  
Clinically Significant ◽  
Early Life Exposures ◽  
The Brain ◽  
Epigenetic Research

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.

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