Epigenetic codes in cognition and behaviour.
TL;DR: Recent findings on the role and mechanisms of epigenetic codes in the brain are described, and their implication in synaptic plasticity, cognitive functions and psychiatric disorders are discussed.
About: This article is published in Behavioural Brain Research.The article was published on 2008-09-01. It has received 260 citations till now. The article focuses on the topics: Epigenetic code & Epigenetics.
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01 May 2011
TL;DR: As scientists have learned more about how the epigenome works, they have begun to develop therapies that may lead to new approaches to treating common human conditions.
Abstract: While our genetic code determines a great deal of who and what we are, it does not act alone. It depends heavily on the epigenome, an elaborate marking of the DNA that controls the genome's functions. Because it is sensitive to the environment, the epigenome is a powerful link and relay between our genes and our surroundings. Epigenetic marks drive biological functions and features as diverse as memory, development, and disease susceptibility; thus, the nurture aspect of the nature/nurture interaction makes essential contributions to our body and behaviors. As scientists have learned more about how the epigenome works, they have begun to develop therapies that may lead to new approaches to treating common human conditions.
12 citations
TL;DR: The hypothesis that the epigenetic dysregulation might be a critical mechanism underlying postoperative cognitive disorder (POCD) is presented and may lead to a new therapeutic strategy of epigenetic intervention for POCD.
12 citations
Additional excerpts
...important role in chromatin remodeling [10]....
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01 Jan 2015
TL;DR: Long-term observational studies should identify molecular, neurophysiological, neuropsychological, and postnatal psychosocial factors involved in the association of maternal anxiety, depression, and stress during pregnancy with offspring self-regulation and may lead to the development of innovative prevention and intervention studies addressing maternal Anxiety, Depression, and/or Stress during pregnancy and its potential consequences.
Abstract: The developmental origins of behavior, health, and disease (DOBHaD) hypothesis examines the short- and long-term effects of environmental conditions early in life on phenotypic variations in behavior, health, and disease. The prenatal and early postnatal periods are times of great opportunity and considerable risk, and their influence can extend over a lifetime. We review human studies on the association of maternal anxiety, depression, and stress during pregnancy with offspring self-regulation from infancy onwards. In the large majority of the studies, this association generally persisted after controlling for postnatal maternal mood and other relevant confounders in the pre- and postnatal periods. Several gestational ages were reported to be vulnerable to the long-term effects of exposure to maternal anxiety, depression, and stress during pregnancy and different mechanisms are likely to operate at different stages. Possible underlying mechanisms (e.g., epigenetic dysregulation) are just starting to be explored. We also discuss postnatal factors (e.g., child–parent attachment) that may modulate the effects of maternal anxiety, depression, and/or stress during pregnancy on offspring self-regulation. Long-term observational studies should identify molecular, neurophysiological, neuropsychological, and postnatal psychosocial factors involved in the association of maternal anxiety, depression, and stress during pregnancy with offspring self-regulation and may lead to the development of innovative prevention and intervention studies addressing maternal anxiety, depression, and/or stress during pregnancy and its potential consequences. Long-term intervention studies are needed for evaluating the efficacy of stress reduction programs to reduce maternal anxiety, depression, and stress during pregnancy and adverse somatic and mental health outcomes in the offspring.
11 citations
TL;DR: Findings indicate that, under certain contexts, HDACIs strengthen memory formation by specifically increasing the associative strength of the CS, not through an increasing motivation to seek reinforcement.
Abstract: Histone deacetylase inhibitors (HDACIs) strengthen memory following fear conditioning and cocaine-induced conditioned place preference. Here, we examined the effects of two nonspecific HDACIs, valproic acid (VPA) and sodium butyrate (NaB), on appetitive learning measured by conditioned stimulus (CS)-induced reinstatement of operant responding. Rats were trained to lever press for food reinforcement and then injected with VPA (50-200 mg/kg, i.p.), NaB (250-1000 mg/kg, i.p.), or saline vehicle (1.0 ml/kg), 2 h before receiving pairings of noncontingent presentation of food pellets preceded by a tone+light cue CS. Rats next underwent extinction of operant responding followed by response-contingent re-exposure to the CS. Rats receiving VPA (100 mg/kg) or NaB (1000 mg/kg) before conditioning displayed significantly higher cue-induced reinstatement than did saline controls. Rats that received either vehicle or VPA (100 mg/kg) before a conditioning session with a randomized relation between presentation of food pellets and the CS failed to show subsequent cue-induced reinstatement with no difference between the two groups. These findings indicate that, under certain contexts, HDACIs strengthen memory formation by specifically increasing the associative strength of the CS, not through an increasing motivation to seek reinforcement.
11 citations
Cites background from "Epigenetic codes in cognition and b..."
...Consistent with our interpretation that NaB and VPA administered before Pavlovian conditioning enhances subsequent cue-induced reinstatement, histone modifying enzymes (and the drugs that modify their activity) have been implicated in many kinds of learning and memory (for reviews see Levenson and Sweatt, 2006; Gräff and Mansuy, 2008)....
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...…NaB and VPA administered before Pavlovian conditioning enhances subsequent cue-induced reinstatement, histone modifying enzymes (and the drugs that modify their activity) have been implicated in many kinds of learning and memory (for reviews see Levenson and Sweatt, 2006; Gräff and Mansuy, 2008)....
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TL;DR: A review of methods available to study protein post-translational modification (PTM) and protein expression based on high-throughput mass spectrometry (MS) can be found in this paper.
Abstract: The complex structural and functional organisation of the brain warrants the application of high-throughput approaches to study its functional alterations in physiological and pathological conditions. Such approaches have greatly benefited from advances in proteomics and genomics, and from their combination with computational modelling. They have been particularly instrumental for the analysis of processes such as the post-translational modification (PTM) of proteins, a critical biological process in the nervous system that remains not well studied. Protein PTMs are dynamic covalent marks that can be induced by activity and allow the maintenance of a trace of this activity. In the nucleus, they can modulate histone proteins and the components of the transcriptional machinery, and thereby contribute to regulating gene expression. PTMs do however need to be tightly controlled for proper chromatin functions. This review provides a synopsis of methods available to study PTMs and protein expression based on high-throughput mass spectrometry (MS), and covers basic concepts of traditional 'shot-gun'-based MS. It describes classical and emerging proteomic approaches such as multiple reaction monitoring and electron transfer dissociation, and their application to the analyses of nuclear processes in the brain.
11 citations
Cites background from "Epigenetic codes in cognition and b..."
...They are also emerging as critical components of enduring effects on brain functions and behaviour induced by early life experience, trauma, hormonal exposure or cognitive activation (Franklin and Mansuy 2009; Graff and Mansuy 2008; McCarthy et al. 2009)....
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References
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TL;DR: The best understood form of long-term potentiation is induced by the activation of the N-methyl-d-aspartate receptor complex, which allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and post Synaptic mechanisms to generate a persistent increase in synaptic strength.
Abstract: Long-term potentiation of synaptic transmission in the hippocampus is the primary experimental model for investigating the synaptic basis of learning and memory in vertebrates. The best understood form of long-term potentiation is induced by the activation of the N-methyl-D-aspartate receptor complex. This subtype of glutamate receptor endows long-term potentiation with Hebbian characteristics, and allows electrical events at the postsynaptic membrane to be transduced into chemical signals which, in turn, are thought to activate both pre- and postsynaptic mechanisms to generate a persistent increase in synaptic strength.
11,123 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...These forms f plasticity reflect respectively, an increase and a decrease in he efficiency of synaptic transmission, and have been extenively studied in the hippocampus, a brain area required for earning and memory (for a review see [30])....
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TL;DR: The surface of nucleosomes is studded with a multiplicity of modifications that can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA.
10,046 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...Chronic xposure to an aggressor results in pronounced social avoidnce, prolonged downregulation of two splice variants of Bdnf, dnfIII and BdnfIV in the hippocampus and increased promoter imethylation of H3K27 [102], a mark of transcriptional represion [20]....
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TL;DR: It is proposed that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
Abstract: Chromatin, the physiological template of all eukaryotic genetic information, is subject to a diverse array of posttranslational modifications that largely impinge on histone amino termini, thereby regulating access to the underlying DNA. Distinct histone amino-terminal modifications can generate synergistic or antagonistic interaction affinities for chromatin-associated proteins, which in turn dictate dynamic transitions between transcriptionally active or transcriptionally silent chromatin states. The combinatorial nature of histone amino-terminal modifications thus reveals a “histone code” that considerably extends the information potential of the genetic code. We propose that this epigenetic marking system represents a fundamental regulatory mechanism that has an impact on most, if not all, chromatin-templated processes, with far-reaching consequences for cell fate decisions and both normal and pathological development.
9,309 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...These nzymes operate both independently and in synergy to establish “histone code”, a highly dynamic and flexible chromatin markng that, in combination with chromatin-associated proteins, etermines the pattern of gene expression in response to given xternal stimuli [24,25]....
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TL;DR: The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development.
Abstract: The character of a cell is defined by its constituent proteins, which are the result of specific patterns of gene expression. Crucial determinants of gene expression patterns are DNA-binding transcription factors that choose genes for transcriptional activation or repression by recognizing the sequence of DNA bases in their promoter regions. Interaction of these factors with their cognate sequences triggers a chain of events, often involving changes in the structure of chromatin, that leads to the assembly of an active transcription complex (e.g., Cosma et al. 1999). But the types of transcription factors present in a cell are not alone sufficient to define its spectrum of gene activity, as the transcriptional potential of a genome can become restricted in a stable manner during development. The constraints imposed by developmental history probably account for the very low efficiency of cloning animals from the nuclei of differentiated cells (Rideout et al. 2001; Wakayama and Yanagimachi 2001). A “transcription factors only” model would predict that the gene expression pattern of a differentiated nucleus would be completely reversible upon exposure to a new spectrum of factors. Although many aspects of expression can be reprogrammed in this way (Gurdon 1999), some marks of differentiation are evidently so stable that immersion in an alien cytoplasm cannot erase the memory. The genomic sequence of a differentiated cell is thought to be identical in most cases to that of the zygote from which it is descended (mammalian B and T cells being an obvious exception). This means that the marks of developmental history are unlikely to be caused by widespread somatic mutation. Processes less irrevocable than mutation fall under the umbrella term “epigenetic” mechanisms. A current definition of epigenetics is: “The study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence” (Russo et al. 1996). There are two epigenetic systems that affect animal development and fulfill the criterion of heritability: DNA methylation and the Polycomb-trithorax group (Pc-G/trx) protein complexes. (Histone modification has some attributes of an epigenetic process, but the issue of heritability has yet to be resolved.) This review concerns DNA methylation, focusing on the generation, inheritance, and biological significance of genomic methylation patterns in the development of mammals. Data will be discussed favoring the notion that DNA methylation may only affect genes that are already silenced by other mechanisms in the embryo. Embryonic transcription, on the other hand, may cause the exclusion of the DNA methylation machinery. The heritability of methylation states and the secondary nature of the decision to invite or exclude methylation support the idea that DNA methylation is adapted for a specific cellular memory function in development. Indeed, the possibility will be discussed that DNA methylation and Pc-G/trx may represent alternative systems of epigenetic memory that have been interchanged over evolutionary time. Animal DNA methylation has been the subject of several recent reviews (Bird and Wolffe 1999; Bestor 2000; Hsieh 2000; Costello and Plass 2001; Jones and Takai 2001). For recent reviews of plant and fungal DNA methylation, see Finnegan et al. (2000), Martienssen and Colot (2001), and Matzke et al. (2001).
6,691 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...ecause of the covalent nature of the binding of methyl groups o the C5 carbon in cytosine, DNA methylation is thought to be he most stable epigenetic mark [9]....
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...DNA methylation is commonly associated with ranscriptional silencing because it can directly inhibit the bindng of transcription factors or regulators, or indirectly recruit ethyl-CpG binding proteins (MBPs), which have repressive hromatin-remodeling functions [9,10]....
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...Most cases of RS are caused by mutaions in the gene coding for methyl-CpG binding protein 2 MeCP2) [62], a member of the MBP family involved in ong-term gene silencing (for a review see [9])....
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TL;DR: Advances in the understanding of the mechanism and role of DNA methylation in biological processes are reviewed, showing that epigenetic mechanisms seem to allow an organism to respond to the environment through changes in gene expression.
Abstract: Cells of a multicellular organism are genetically homogeneous but structurally and functionally heterogeneous owing to the differential expression of genes. Many of these differences in gene expression arise during development and are subsequently retained through mitosis. Stable alterations of this kind are said to be 'epigenetic', because they are heritable in the short term but do not involve mutations of the DNA itself. Research over the past few years has focused on two molecular mechanisms that mediate epigenetic phenomena: DNA methylation and histone modifications. Here, we review advances in the understanding of the mechanism and role of DNA methylation in biological processes. Epigenetic effects by means of DNA methylation have an important role in development but can also arise stochastically as animals age. Identification of proteins that mediate these effects has provided insight into this complex process and diseases that occur when it is perturbed. External influences on epigenetic processes are seen in the effects of diet on long-term diseases such as cancer. Thus, epigenetic mechanisms seem to allow an organism to respond to the environment through changes in gene expression. The extent to which environmental effects can provoke epigenetic responses represents an exciting area of future research.
5,760 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...ot be explained by changes in the DNA sequence itself [3] reviewed in [4,5])....
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