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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TL;DR: These studies indicate that SES is an important predictor of neurocognitive performance, particularly of language and executive function, and that S ES differences are found in neural processing even when performance levels are equal.
1,258 citations
TL;DR: An epigenetic molecular mechanism potentially underlying lifelong and transgenerational perpetuation of changes in gene expression and behavior incited by early abuse and neglect is highlighted.
1,176 citations
TL;DR: The results of this work suggest that patterns of transcription regulation represent the molecular signatures of long-term synaptic changes and memory formation.
Abstract: Transcription is a molecular requisite for long-term synaptic plasticity and long-term memory formation. Thus, in the last several years, one main interest of molecular neuroscience has been the identification of families of transcription factors that are involved in both of these processes. Transcription is a highly regulated process that involves the combined interaction and function of chromatin and many other proteins, some of which are essential for the basal process of transcription, while others control the selective activation or repression of specific genes. These regulated interactions ultimately allow a sophisticated response to multiple environmental conditions, as well as control of spatial and temporal differences in gene expression. Evidence based on correlative changes in expression, genetic mutations, and targeted molecular inhibition of gene expression have shed light on the function of transcription in both synaptic plasticity and memory formation. This review provides a brief overview ...
902 citations
Cites background from "Epigenetic codes in cognition and b..."
...[From Gräff and Mansuy (82), with permission from Elsevier....
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...[From Gräff and Mansuy (82), with permission from Elsevier.]...
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TL;DR: As histone acetylation and cognitive functions can be pharmacologically restored by histone deacetylase inhibitors, this epigenetic modification might constitute a molecular memory aid on the chromatin and, by extension, a new template for therapeutic interventions against cognitive frailty.
Abstract: Long-lasting memories require specific gene expression programmes that are, in part, orchestrated by epigenetic mechanisms. Of the epigenetic modifications identified in cognitive processes, histone acetylation has spurred considerable interest. Whereas increments in histone acetylation have consistently been shown to favour learning and memory, a lack thereof has been causally implicated in cognitive impairments in neurodevelopmental disorders, neurodegeneration and ageing. As histone acetylation and cognitive functions can be pharmacologically restored by histone deacetylase inhibitors, this epigenetic modification might constitute a molecular memory aid on the chromatin and, by extension, a new template for therapeutic interventions against cognitive frailty.
506 citations
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TL;DR: This Review develops four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram, and proposes that findings from 'capture' studies represent considerable progress in allowing us to observe, erase and express the engrams.
Abstract: Many attempts have been made to localize the physical trace of a memory, or engram, in the brain However, until recently, engrams have remained largely elusive In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram Recent 'capture' studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram
464 citations
References
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TL;DR: In this paper, the authors investigated whether PHD finger mutations are present in Rubinstein-Taybi syndrome (RTS) patients and found that deletion of the PHD-type zinc finger is sufficient to cause RTS.
Abstract: Disruption of one copy of the human CREB binding protein (CBP or CREBBP) gene leads to the Rubinstein-Taybi syndrome (RTS), a developmental disorder characterized by retarded growth and mental functions, broad thumbs, broad big toes and typical facial abnormalities. The CREB binding protein (CBP) is an essential transcriptional coactivator for many different transcription factors. CBP has the intrinsic ability to acetylate histones and other proteins, which is regarded as an important step in transcription activation. In vitro studies have shown that this enzymatic activity critically depends on the integrity of a plant homeodomain (PHD)-type zinc finger in the HAT domain of CBP. We therefore investigated whether PHD finger mutations are present in RTS patients. Mutational analysis of 39 patients revealed eight novel heterozygous mutations in the HAT domain of CBP, one of which alters a conserved PHD finger amino acid (E1278K), while a second mutation deletes exon 22, which encodes the central region of the PHD finger. Functional analysis of these RTS-associated PHD finger mutants showed that they lacked in vitro acetyltransferase activity towards histones and CBP itself and displayed reduced coactivator function for the transcription factor CREB. Importantly, in EBV-transformed lymphoblastoid cells from the exon 22 deletion patient we found approximately 50% less endogenous CBP HAT activity. These findings therefore underscore the functional importance of the PHD finger in vivo and imply that reduction of CBP HAT activity, as exemplified here by disruption of the PHD finger, is sufficient to cause RTS.
128 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...[58] Kalkhoven E, Roelfsema JH, Teunissen H, den Boer A, Ariyurek Y, Zantema A, et al....
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TL;DR: This mouse knock-out is the first example of an animal model of human mental retardation with impaired learning and memory performance and increased LTP, and the data suggest thatIncreased LTP may be a mechanism that leads to impaired cognitive processing as well.
Abstract: FRAXE mental retardation results from expansion and methylation of a CCG trinucleotide repeat located in exon 1 of the X-linked FMR2 gene, which results in transcriptional silencing. The product of FMR2 is a member of a family of proteins rich in serine and proline, members of which have been associated with transcriptional activation. We have developed a murine Fmr2 gene knock-out model by replacing a fragment containing parts of exon 1 and intron 1 with the Escherichia coli lacZ gene, placing lacZ under control of the Fmr2 promoter. Expression of lacZ in the knock-out animals indicates that Fmr2 is expressed in several tissues, including brain, bone, cartilage, hair follicles, lung, tongue, tendons, salivary glands, and major blood vessels. In the CNS, Fmr2 expression begins at the time that cells in the neuroepithelium differentiate into neuroblasts. Mice lacking Fmr2 showed a delay-dependent conditioned fear impairment. Long-term potentiation (LTP) was found to be enhanced in hippocampal slices of Fmr2 knock-out compared with wild-type littermates. To our knowledge, this mouse knock-out is the first example of an animal model of human mental retardation with impaired learning and memory performance and increased LTP. Thus, although a number of studies have suggested that diminished LTP is associated with memory impairment, our data suggest that increased LTP may be a mechanism that leads to impaired cognitive processing as well.
112 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...Although such dissociation between mpaired memory and enhanced LTP was previously reported [74] and references therein), the mechanisms underlying these lterations and their biological implication remain unknown....
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...Mammalian synaptic plasticity The most prominent forms of synaptic plasticity in mamals are long-term potentiation (LTP) and LTD....
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...In mice, an FMR2 deficiency nduced by gene knock-out impairs spatial memory, however, t enhances LTP [74]....
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...Treatment of such slices with he HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) meliorates late-phase LTP. Importantly, a similar effect is bserved in wild-type rats, in which administration of the HDAC nhibitors trichostatin A (TSA) or sodium butyrate enhances the nduction of LTP in the hippocampus [36], suggesting a causal ink between histone acetylation and LTP....
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...LTP is nhanced in eed+/− mice and decreased in MII+/− mice, which orrelates with H4 hypoacetylation of several residues in MII+/− ice [38]....
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TL;DR: Recent reports on two transcriptional regulators have begun to reveal how epigenetics and neuronal activity act to modulate the program of gene expression required for synaptic development and function.
103 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...A deficiency in MeCP2 also orrelated with increased overall acetylation of H3 in the cereral cortex and cerebellum [69], further strengthening the idea hat MeCP2 exerts its repressive function, in part, by recruitng histone-modifying enzymes that reinforce the compaction f chromatin [70]....
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95 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...[47] Holliday R....
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...In 999, Holliday [47] followed this concept, and refined the idea f epigenetics to the process of DNA methylation....
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TL;DR: The findings suggest that betelnut (Areca) consumption may be diabetogenic and induce an inheritable abnormality in mice with an increased incidence of foregut cancers related to betel-nut nitrosamines.
Abstract: Many mutagenic nitroso compounds are also diabetogenic. Betel-nut (Areca catechu) chewing populations have an increased incidence of foregut cancers related to betel-nut nitrosamines which suggests that betel consumption could be diabetogenic. Young adult CD1 mice with a low spontaneous incidence of diabetes were fed betel nut in standard feed for 2–6 days. Single point (90 min) intra-peritoneal glucose tolerance tests were used to follow glucose tolerance up to 6 months of age. Glucose intolerance was defined as over 3 SD above mean control values. Glucose intolerance was found in 3 of 51 male and 4 of 33 female adult mice which were fed the betel diet (p<0.01). Studies on the progeny of these mice are presented separately for animals studied in Aberdeen (Group 1) and London (Group 2). In matings of Group 1 betel-fed parents glucose intolerance was found in 4 of 25 male and 1 of 22 female F1 offspring, with significant hyperglycaemia in F1 males born to hyperglycaemic but not to normoglycaemic mothers (p<0.01). In the F2 generation 4 of 23 males and 1 of 16 females and in the F3 generation 1 of 16 males and 0 of 20 females were glucose intolerant. In the Group 2 studies where betel-fed parents were mated to normal controls glucose intolerance was found in 10 of 35 male and 10 of 33 female Fl progeny (p<0.005), and mean islet areas were increased in offspring of betel-fed parents (p<0.001). The total incidence of glucose intolerance in Fl progeny from studies in Groups 1 and 2 was 14 of 60 males and 11 of 55 females (p<0.005). Insulin dependence did not develop in the glucose-intolerant betel-fed animals or their descendants; affected animals appearing well built and active. The development of glucose intolerance in F1 offspring was not dependent on maternal glucose intolerance or on maternal betel-feeding, and 90-min glucose levels of F1 offspring were directly related to paternal but not to maternal glycaemia (p<0.01). Our findings suggest that betelnut (Areca) consumption may be diabetogenic and induce an inheritable abnormality. The hypothesis is of interest in view of the widespread habit of betel consumption and of the strategies known to inhibit the induction of experimental diabetes by diabetogenic nitroso compounds.
95 citations
"Epigenetic codes in cognition and b..." refers result in this paper
...In mice, imilar results were obtained in F1 and F2 males born to hyperlycemic fathers but not in females [135], indicating paternal ermline inheritance....
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