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941.
Korosi A Naninck EF Oomen CA Schouten M Krugers H Fitzsimons C Lucassen PJ 《Behavioural brain research》2012,227(2):400-409
Early life is a period of unique sensitivity during which experience can confer enduring effects on brain structure and function. During early perinatal life the quality of the surrounding environment and experiences, in particular the parent-child relationship, is associated with emotional and cognitive development later in life. For instance, adverse early-life experience is correlated with an increased vulnerability to develop psychopathologies and aging-related cognitive decline. These are thought to be mediated by acute and long-lasting effects on the, at that time still developing, stress-neuroendocrine and cognitive systems. Adult hippocampal neurogenesis is involved in learning and memory while both regulation of the stress response as well as early-life stress is known to permanently reduce neurogenesis, and to be implicated in these functional deficits.In order to increase our understanding of the influence of the perinatal environment on the long-lasting programming of neurogenesis, we here discuss immediate and lasting effects of various adverse early-life experiences on hippocampal neurogenesis and the associated behavioral alterations. Considering the persistence of these effects, the underlying molecular mechanisms, with focus on the potential epigenetic mechanisms will be discussed as well. Finally, special attention will be paid to the prominent sex differences in early-life stress-induced alterations in neurogenesis. 相似文献
942.
背景 组蛋白修饰是表观遗传学的一项重要内容.近年来研究证实组蛋白修饰调节异常在病理性疼痛的发生发展中起重要作用. 目的 阐述组蛋白修饰调节异常在病理性疼痛产生和维持中作用的研究进展,为病理性疼痛的治疗提供新思路. 内容 讨论组蛋白修饰、组蛋白乙酰化、组蛋白甲基化与病理性疼痛的关系以及组蛋白去乙酰化酶(histonedeacetylase,HDAC)抑制剂对病理性疼痛的治疗作用. 趋向 鉴于组蛋白修饰调节异常在病理性疼痛的重要作用,组蛋白修饰的调节将为病理性疼痛的治疗提供新的策略. 相似文献
943.
系统性红斑狼疮是一种累及全身多器官系统的自身免疫性疾病,其发病机制尚不明确.表观遗传学是指发生在基因表达水平的可遗传的变化,但不涉及基因序列的改变.其涉及的机制主要有DNA甲基化、组蛋白修饰、microRNA等.研究显示,表观遗传学异常与系统性红斑狼疮发病密切相关.主要阐述DNA甲基化、组蛋白修饰和microRNA在系统性红斑狼疮发病中的作用. 相似文献
944.
Daniela Zuccarello Ugo Sorrentino Valeria Brasson Loris Marin Chiara Piccolo Antonio Capalbo Alessandra Andrisani Matteo Cassina 《Journal of assisted reproduction and genetics》2022,39(4):801
Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal–fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders. 相似文献
945.
甲基化CpG结合蛋白家族是一类能与甲基化CpG岛特异性结合并相互作用的蛋白质,它们具有共同的甲基化CpG结合域(methyl-CpG-binding domain , MBD),并与组蛋白去乙酰化酶、组蛋白乙酰化酶、组蛋白甲基化酶和DNA甲基转移酶有着广泛的联系,将DNA甲基化、组蛋白修饰和染色质构象改变紧密联系起来,在X染色体失活、印记基因沉默和肿瘤细胞抑癌基因沉默中发挥关键性的枢纽作用。本文综述了甲基化CpG结合蛋白家族的研究历史和最新的一些研究进展以及它们在基因抑制中所起的重要作用。 相似文献
946.
947.
Richard D. Emes Harry Clifford Kim E. Haworth William E. Farrell Anthony A. Fryer William D. Carroll Khaled M. K. Ismail 《Epilepsia》2013,54(1):e16-e19
Antiepileptic drugs (AEDs) can lower maternal folate and increase maternal homocysteine levels, which are known to affect the methyl cycle and hence DNA methylation levels. The influence of in utero exposure to AEDs on fetal DNA methylation was investigated. Genome‐wide fetal epigenomic profiles were determined using the Infinium 27K BeadArray from Illumina (San Diego, CA, U.S.A.). The Infinium array measures approximately 27,000 CpG loci associated with 14,496 genes at single‐nucleotide resolution. Eighteen cord blood samples (nine samples from babies exposed to AEDs and nine controls) from otherwise uncomplicated pregnancies were compared. Unsupervised hierarchic clustering was used to compare the calculated methylation profiles. A clear distinction between the methylation profiles of samples from babies exposed to AEDs in utero compared with controls was detected. These data provide evidence of an epigenetic effect associated with antenatal AED and high‐dose folate supplementation during pregnancy. The differences in fetal DNA methylation of those exposed to AEDs shows that a genome‐wide effect of methylation is evident. In addition, the epigenetic changes observed appear to be, in this limited sample, independent of extremes of birth weight centiles. These preliminary data highlight possible mechanisms by which AEDs might influence fetal outcomes and the potential of optimizing AED‐specific folate supplementation regimens to offset these effects. 相似文献
948.
949.
950.
Why exactly some individuals develop autoimmune disorders remains unclear. The broadly accepted paradigm is that genetic susceptibility results in some break in immunological tolerance, may enhance the availability of autoantigens, and may enhance inflammatory responses. Some environmental insults that occur on this background of susceptibility may then contribute to autoimmunity. In this review we discuss some aspects related to inhibitory signaling and rare genetic variants, as well as additional factors that might contribute to autoimmunity including the possible role of clonal somatic mutations, the role of epigenetic events and the contribution of the intestinal microbiome. Genetic susceptibility alleles generally contribute to the loss of immunological tolerance, the increased availability of autoantigens, or an increase in inflammation. Apart from common genetic variants, rare loss-of-function genetic variants may also contribute to the pathogenesis of autoimmunity. Studies of an inhibitory signaling pathway in B cells helped identify a negative regulatory enzyme called sialic acid acetyl esterase. The study of rare genetic variants of this enzyme provides an illustrative example showing the importance of detailed functional analyses of variant alleles and the need to exclude functionally normal common or rare genetic variants from analysis. It has also become clear that pathways that are functionally impacted by either common or rare defective variants can also be more significantly compromised by gene expression changes that may result from epigenetic alterations. Another important and evolving area that has been discussed relates to the role of the intestinal microbiome in influencing helper T cell polarization and the development of autoimmunity. 相似文献