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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10 Mar 2019
TL;DR: کچ هدي شيپ هنيمز و فده : لولس اه ي NG2 هب ناونع پ ی زاس ش لowsi اعلاح هعلاطم زا فdه .
Abstract: کچ هدي شيپ هنيمز و فده : لولس اه ي NG2 هب ناونع پ ی زاس ش لولس اه ي لا ی سوردندوگ ی اراد و هدوب ت ي نورون هدننک تظافح شقن ی م ی رضاح هعلاطم زا فده .دنشاب سررب ی اقم و ی هس ثأت ی ر رمت هتفه راهچ ی تخا ن ی را ي لومعم ی پ و ی چ ی حوطس رب هد NG2 زغم تر اه ي و داژن ملاس رن ی .دوب راتس شور و داوم راک : 30 رس و داژن تر ی زا سپ غلاب راتس ی انشآ هتفه ک یی حم اب ی امزآ ط ی هاگش هب تروص فداصت ی رمت هورگ هس هب ی تخا ن ی را ي ور ي س راود خرچ ،هدا رمت ی تخا ن ی را ي ور ي پ راود خرچ ی چ ی لرتنک هورگ و هد میسقت يدنب .دندش هورگ اه ي رمت ی ن ی هتفه راهچ تدم هب هب روط تخا ی را ي لاعف ماجنا هب ی دنتخادرپ ت . شور زا لاا ی ارب از ي هزادنا يریگ NG2 درگ هدافتسا زغم ی سررب .د ی م توافت ی گنا ی ن لحت شور اب اه ی راو ل ی سنا ی ک هفرط قعت نومزآ و ی ب ی کوت ی زا هدافتسا اب ، مرن فا راز SPSS هخسن 20 .تفرگ تروص هتفاي اه رمت ماجنا : ی تخا تان ی را ي ور ي ) هداس راود خرچ P=0/03 ور و ( ي پ راود خرچ ی چ ی هد ) P=0/001 غت ( یی نعم ر ی راد ي حوطس رد NG2 تر زغم اه ي داژن ملاس و ی نچمه .تشاد راتس ی ب ن ی رمت عون ود ن ی نعم توافت ن ی راد ي ) دشن هدهاشم P=0/05 .( هجيتن و ثحب :يريگ اتن ساسا رب ی ج هب تسد هدمآ رمت هتفه راهچ ، ی تخا ن ی را ي پ راود خرچ لدم ود رد ی چ ی لومعم و هد ی ازفا ی نعم ش ی راد ي د حوطس ر NG2 زغم تر اه ي و داژن ملاس رن ی ا راتس ی .درک داج تنرد ی هج ا زا ی رمت شور ود ن ی ن ی تهج ، ثأت ی راذگر ي ور رب تبثم ي ازفا ی ش تیسوردندوگیلا اه تر رد اه ي م ملاس ی ت ناو رمت شور و درک هدافتسا ی تخا ن ی را ي پ ی چ ی شخبرثا هد ی ب ی رتش ي .دراد هژاوديلک :اه رمت ی تخا ن ی را ي لومعم راود خرچ ، ی پ راود خرچ ، ی چ ی ،هد NG2
1 citations
10 Dec 2014
TL;DR: In this paper , the use of natural products as epidrugs to treat neurodegenerative disorders (NDDs) has been discussed in order to explore the epigenetic effects and benefits of functional foods and natural bioproducts.
Abstract: Neurodegenerative disorders (NDDs) are major health issues in Western countries. Despite significant efforts, no effective therapeutics for NDDs exist. Several drugs that target epigenetic mechanisms (epidrugs) have been recently developed for the treatment of NDDs, and several of these are currently being tested in clinical trials. Furthermore, various bioproducts have shown important biological effects for the potential prevention and treatment of these disorders. Here, we review the use of natural products as epidrugs to treat NDDs in order to explore the epigenetic effects and benefits of functional foods and natural bioproducts on neurodegeneration.
TL;DR: In this paper , differences in global DNA methylation (5mC) levels in serum samples from patients during the initial-and the follow-up visits were examined, revealing that 5mC has a diagnostic value as a biomarker across different pathologies.
Abstract: DNA methylation remains an under-recognized diagnostic biomarker for several diseases, including neurodegenerative disorders. In this study, we examined differences in global DNA methylation (5mC) levels in serum samples from patients during the initial- and the follow-up visits. Each patient underwent a blood analysis and neuropsychological assessments. The analysis of 5mC levels revealed two categories of patients; Group A who, during the follow-up, had increased 5mC levels, and Group B who had decreased 5mC levels. Patients with low Fe-, folate-, and vitamin B12- levels during the initial visit showed increased levels of 5mC after treatment when assessed during the follow-up. During the follow-up, 5mC levels in Group A patients increased after treatment for hypovitaminosis with the nutraceutical compounds Animon Complex and MineraXin Plus. 5mC levels were maintained during the follow-up in Group A patients treated for neurological disorders with the bioproducts AtreMorine and NeoBrainine. There was a positive correlation between 5mC levels and MMSE scores, and an inverse correlation between 5mC and ADAS-Cog scores. This expected correlation was observed in Group A patients only. Our study appears to indicate that 5mC has a diagnostic value as a biomarker across different pathologies.
Dissertation•
01 Jan 2017
TL;DR: The studies here presented contributed to advance scientific knowledge of the role of epigenetic factors in regulating synaptic, cognitive and neurodevelopmental processes, that can be used for future studies related to KS and the epigenetic regulation of nervous system function and development.
Abstract: The contribution of epigenetic factors in controlling the expression of genetic programs related to cognition
and development posed a novel fascinating research challenge. Epigenetic factors, in general, are involved
in translating environmental stimuli and transducing a controlled response via modulation of gene
expression. In the recent years, epigenetic mechanisms were described to be required for neurobiological
processes like synaptic plasticity, cognition, brain development and psychiatric disorders. Interestingly,
mutation in genes that encode for epigenetic factors were described to be causative for numerous
neurodevelopmental disorders such as Intellectual disabilities and Autism spectrum disorders. In Nijmegen,
Kleefstra and collaborators, in the last decade described for the first time a mutation in the Euchromatic
histone methyl-transferase 1 (EHMT1) gene, that is causative for a neurodevelopmental disorder
denominated as Kleefstra syndrome (KS).
The findings presented in this research thesis relate to functional studies of the KS gene EHMT1 in
regulating synaptic homeostasis and hippocampal pattern separation. By combining a diverse array of
genetic and pharmacological manipulations of EHMT1 expression and function in a construct-validated
mouse model for KS and in neurons derived from human pluripotent stem cells (hiPSCs) directly from KS-
patients, new roles of EHMT1 function in regulating homeostatic synaptic scaling and pattern separation in
the hippocampus are described. The findings here outlined extended our understanding of the
pathophysiology related to KS at a molecular and physiological level. In parallel, the studies here presented
contributed to advance scientific knowledge of the role of epigenetic factors in regulating synaptic, cognitive
and neurodevelopmental processes, that can be used for future studies related to KS and the epigenetic
regulation of nervous system function and development.
Cites background from "Epigenetic codes in cognition and b..."
...Most of the studies on epigenetics in cognition have focused on DNA methylation and histone H3 (de)-acetylation and have been summarized in recent reviews (Gräff and Mansuy, 2008; Gräff et al., 2012b; Miller et al., 2010; Penney and Tsai, 2014; Zovkic et al., 2013)....
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...In particular, histone H3 methylation has been shown to modulate enduring changes in gene expression to regulate memory formation and neural plasticity (Sharma et al., 2016; Fischer et al., 2007; Gräff and Mansuy, 2008; Gupta et al., 2010; GuptaAgarwal et al., 2012; 2014; Lubin et al., 2011; Parkel et al., 2013)....
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...…H3 methylation has been shown to modulate enduring changes in gene expression to regulate memory formation and neural plasticity (Sharma et al., 2016; Fischer et al., 2007; Gräff and Mansuy, 2008; Gupta et al., 2010; GuptaAgarwal et al., 2012; 2014; Lubin et al., 2011; Parkel et al., 2013)....
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...Most of the studies on epigenetics in cognition have focused on DNA methylation and histone H3 (de)-acetylation and have been summarized in recent reviews (Gräff and Mansuy, 2008; Gräff et al., 2012b; Miller et al., 2010; Penney and Tsai, 2014; Zovkic et al., 2013)....
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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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