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
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324 citations
TL;DR: A family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation is reported.
Abstract: Epimutations in the germline, such as methylation of the MLH1 gene, may contribute to hereditary cancer syndrome in human, but their transmission to offspring has never been documented. Here we report a family with inheritance, in three successive generations, of germline allele-specific and mosaic hypermethylation of the MSH2 gene, without evidence of DNA mismatch repair gene mutation. Three siblings carrying the germline methylation developed early-onset colorectal or endometrial cancers, all with microsatellite instability and MSH2 protein loss. Clonal bisulfite sequencing and pyrosequencing showed different methylation levels in different somatic tissues, with the highest level recorded in rectal mucosa and colon cancer tissue, and the lowest in blood leukocytes. This mosaic state of germline methylation with different tissue distribution could act as the first hit and provide a mechanism for genetic disease inheritance that may deviate from the mendelian pattern and be overlooked in conventional leukocyte-based genetic diagnosis strategy.
313 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...The first study describes that hypermethylation of the NA mismatch repair gene mutS homologue 2 (MSH2) across hree generations in somatic tissue can be inherited through the ermline [137]....
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..., nonpolyposis colorectal cancer, might also be of pigenetic origin [137,138], although this remains controversial 139-141]....
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...[137] Chan TL, Yuen ST, Kong CK, Chan YW, Chan ASY, Ng WF, et al....
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...Non-adaptive examples include male infertility following inclozolin exposure during gonadal sex determination [131] r nonpolyposis colorectal cancer [137,138]....
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TL;DR: CBP +/- mice would be an excellent model for the study of the role of CBP in development and memory storage mechanisms, and studies with step-through-type passive avoidance tests and with fear conditioning test showed that mice were deficient in long-term memory (LTM).
Abstract: A mouse model of Rubinstein-Taybi syndrome (RTS) was generated by an insertional mutation into the cyclic AMP response element-binding protein (CREB)-binding protein (CBP) gene. Heterozygous CBP-deficient mice, which had truncated CBP protein (residues 1-1084) containing the CREB-binding domain (residues 462-661), showed clinical features of RTS, such as growth retardation (100%), retarded osseous maturation (100%), hypoplastic maxilla with narrow palate (100%), cardiac anomalies (15%) and skeletal abnormalities (7%). Truncated CBP is considered to have been acting during development as a dominant-negative inhibitor to lead to the phenotypes of RTS in mice. Our studies with step-through-type passive avoidance tests and with fear conditioning test showed that mice were deficient in long-term memory (LTM). In contrast, short-term memory (STM) appeared to be normal. These results implicate a crucial role for CBP in mammalian LTM. Our CBP +/- mice would be an excellent model for the study of the role of CBP in development and memory storage mechanisms.
308 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...Several mouse models with CBP mutations were generated nd confirmed the involvement of CBP in the molecular mechnisms of the disease [39,50,60,61]....
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...[61] Oike Y, Hata A, Mamiya T, Kaname T, Noda Y, Suzuki M, et al....
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TL;DR: The presence of the very selective D1 receptor blocker SCH 23390 at a concentration of 0.1 microM during tetanization with 3 trains of 100 impulses resulted in a prevention of late LTP stages (greater than 1-2 h).
302 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...[32] Frey U, Matthies H, Reymann KG, Matthies H....
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TL;DR: Cloning and characterization of FMR2 is reported, demonstrating that this is a gene associated with the CpG island adjacent to FRAXE and contributes to F RAXE-associated mild mental retardation.
Abstract: Five folate-sensitive fragile sites have been characterized at the molecular level (FRAXA, FRAXE, FRAXF, FRA16A and FRA11B). Three of them (FRAXA, FRAXE and FRA11B) are associated with clinical problems, and two of the genes (FMR1 in FRAXA and CBL2 in FRA11B) have been identified. All of these fragile sites are associated with (CCG)n/(CGG)n triplet expansions which are hypermethylated beyond a critical size. FRAXE is a rare folate sensitive fragile site only recently recognized. Its cytogenetic expression was found to involve the amplification of a (CCG)n repeat adjacent to a CpG island. Normal alleles vary from 6 to 25 copies. Expansions of greater than 200 copies were found in FRAXE expressing males and their FRAXE associated CpG island was fully methylated. An association of FRAXE expression with concurrent methylation of the CpG island and mild non-specific mental handicap in males has been reported by several groups. We now report the cloning and characterization of a gene (FMR2) adjacent to FRAXE. Elements of FMR2 were initially identified from sequences deleted from a developmentally delayed boy. We correlate loss of FMR2 expression with (CCG)n expansion at FRAXE, demonstrating that this is a gene associated with the CpG island adjacent to FRAXE and contributes for FRAXE-associated mild mental retardation.
300 citations
"Epigenetic codes in cognition and b..." refers background in this paper
...[72] Gecz J, Gedeon AK, Sutherland GR, Mulley JC....
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