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Mecp2

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https://www.readbyqxmd.com/read/28814546/mglu7-potentiation-rescues-cognitive-social-and-respiratory-phenotypes-in-a-mouse-model-of-rett-syndrome
#1
Rocco G Gogliotti, Rebecca K Senter, Nicole M Fisher, Jeffrey Adams, Rocio Zamorano, Adam G Walker, Anna L Blobaum, Darren W Engers, Corey R Hopkin, J Scott Daniels, Carrie K Jones, Craig W Lindsley, Zixiu Xiang, P Jeffrey Conn, Colleen M Niswender
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. The cognitive impairments seen in mouse models of RTT correlate with deficits in long-term potentiation (LTP) at Schaffer collateral (SC)-CA1 synapses in the hippocampus. Metabotropic glutamate receptor 7 (mGlu7) is the predominant mGlu receptor expressed presynaptically at SC-CA1 synapses in adult mice, and its activation on GABAergic interneurons is necessary for induction of LTP. We demonstrate that pathogenic mutations in MECP2 reduce mGlu7 protein expression in brain tissue from RTT patients and in MECP2-deficient mouse models...
August 16, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28813484/d-cycloserine-improves-synaptic-transmission-in-an-animal-mode-of-rett-syndrome
#2
Elisa S Na, Héctor De Jesús-Cortés, Arlene Martinez-Rivera, Zeeba D Kabir, Jieqi Wang, Vijayashree Ramesh, Yasemin Onder, Anjali M Rajadhyaksha, Lisa M Monteggia, Andrew A Pieper
Rett syndrome (RTT), a leading cause of intellectual disability in girls, is predominantly caused by mutations in the X-linked gene MECP2. Disruption of Mecp2 in mice recapitulates major features of RTT, including neurobehavioral abnormalities, which can be reversed by re-expression of normal Mecp2. Thus, there is reason to believe that RTT could be amenable to therapeutic intervention throughout the lifespan of patients after the onset of symptoms. A common feature underlying neuropsychiatric disorders, including RTT, is altered synaptic function in the brain...
2017: PloS One
https://www.readbyqxmd.com/read/28796949/mecp2-and-ctcf-enhancing-the-cross-talk-of-silencers
#3
Juan Ausio, Philippe T Georgel
This paper provides a brief introductory review of the most recent advances in our knowledge about structural and functional aspects of two transcriptional regulators: the methyl-CpG protein binding 2 (MeCP2), a protein whose mutated forms are involved in Rett syndrome and CCCTC-binding factor (CTCF), a constitutive transcriptional insulator. This is followed by a description of the post-translational modifications (PTMs) affecting these two proteins and an analysis of their known interacting partners. A special emphasis is placed on the recent studies connecting these two proteins focusing on the still poorly understood potential structural and functional interactions between the two of them on the chromatin substrate...
August 10, 2017: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28795659/role-of-mycotoxins-in-the-pathobiology-of-autism-a-first-evidence
#4
Barbara De Santis, Carlo Brera, Alessandra Mezzelani, Sabina Soricelli, Francesca Ciceri, Giorgio Moretti, Francesca Debegnach, Maria Clara Bonaglia, Laura Villa, Massimo Molteni, Maria Elisabetta Raggi
OBJECTIVES: Gene-environment interaction is an emerging hypothesis to expound not only the autism pathogenesis but also the increased incidence of neurodevelopmental disorders (such as autistic spectrum disorder, attention-deficit, hyperactivity disorder). Among xenobiotics, mycotoxins are worldwide contaminants of food that provoke toxicological effects, crucially resembling several symptoms associated with autism such as oxidative stress, intestinal permeability, and inflammation. Here, we focused on a group of mycotoxins to test their role in the manifestation of autism, try to explain their mechanism of action, and discuss possible preventive and therapeutic interventions...
August 10, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28767600/mecp2-expression-in-gastric-cancer-and-its-correlation-with-clinical-pathological-parameters
#5
Jing Zhang, Junmei Zhao, Ning Gao, Yanfeng Wang, Yani Chen, Jiming Han
This study is to investigate the expression of methyl CpG binding protein 2 (MECP2) in gastric cancer (GC) and its clinical significance.Expression of MECP2 was analyzed in 69 cases of GC tissues and 12 paracancerous tissues, either by qRT-PCR at the mRNA level or by Western blot and immunochemistry at the protein level. The correlation of MECP2 expression with clinicopathological parameters was analyzed in the 69 GC patients, and validated in data from the TCGA database. The effect of MECP2 expression on survival was also investigated...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28760966/neuronal-cytoskeletal-gene-dysregulation-and-mechanical-hypersensitivity-in-a-rat-model-of-rett-syndrome
#6
Aritra Bhattacherjee, Ying Mu, Michelle K Winter, Jennifer R Knapp, Linda S Eggimann, Sumedha S Gunewardena, Kazuto Kobayashi, Shigeki Kato, Dora Krizsan-Agbas, Peter G Smith
Children with Rett syndrome show abnormal cutaneous sensitivity. The precise nature of sensory abnormalities and underlying molecular mechanisms remain largely unknown. Rats with methyl-CpG binding protein 2 (MeCP2) mutation, characteristic of Rett syndrome, show hypersensitivity to pressure and cold, but hyposensitivity to heat. They also show cutaneous hyperinnervation by nonpeptidergic sensory axons, which include subpopulations encoding noxious mechanical and cold stimuli, whereas peptidergic thermosensory innervation is reduced...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28759023/mecp2-a-target-of-mir-638-facilitates-gastric-cancer-cell-proliferation-through-activation-of-the-mek1-2-erk1-2-signaling-pathway-by-upregulating-git1
#7
L Y Zhao, D D Tong, M Xue, H L Ma, S Y Liu, J Yang, Y X Liu, B Guo, L Ni, L Y Liu, Y N Qin, L M Wang, X G Zhao, C Huang
Methyl-CpG binding protein 2 (MeCP2) is involved in the carcinogenesis and progression of multiple types of cancer. However, its precise role in gastric cancer (GC) and the relevant molecular mechanism remain unknown. In the present study, we found that miR-638 levels were lower in GC tissues and GC cell lines than in adjacent normal tissues and normal gastric epithelial cell lines, respectively. Low miR-638 levels were associated with poor tumor differentiation, tumor size and lymph node metastasis. MeCP2 expression levels were higher in GC tissues than in adjacent normal tissues...
July 31, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28754949/cell-permeable-nanobodies-for-targeted-immunolabelling-and-antigen-manipulation-in-living-cells
#8
Henry D Herce, Dominik Schumacher, Anselm F L Schneider, Anne K Ludwig, Florian A Mann, Marion Fillies, Marc-André Kasper, Stefan Reinke, Eberhard Krause, Heinrich Leonhardt, M Cristina Cardoso, Christian P R Hackenberger
Functional antibody delivery in living cells would enable the labelling and manipulation of intracellular antigens, which constitutes a long-thought goal in cell biology and medicine. Here we present a modular strategy to create functional cell-permeable nanobodies capable of targeted labelling and manipulation of intracellular antigens in living cells. The cell-permeable nanobodies are formed by the site-specific attachment of intracellularly stable (or cleavable) cyclic arginine-rich cell-penetrating peptides to camelid-derived single-chain VHH antibody fragments...
August 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28751857/the-bdnf-val-66-met-polymorphism-affects-neuronal-morphology-and-synaptic-transmission-in-cultured-hippocampal-neurons-from-rett-syndrome-mice
#9
Xin Xu, Jordi Garcia, Rachel Ewalt, Shelly Nason, Lucas Pozzo-Miller
Brain-derived neurotrophic factor (Bdnf) has been implicated in several neurological disorders including Rett syndrome (RTT), an X-linked neurodevelopmental disorder caused by loss-of-function mutations in the transcriptional modulator methyl-CpG-binding protein 2 (MECP2). The human BDNF gene has a single nucleotide polymorphism (SNP)-a methionine (met) substitution for valine (val) at codon 66-that affects BDNF's trafficking and activity-dependent release and results in cognitive dysfunction. Humans that are carriers of the met-BDNF allele have subclinical memory deficits and reduced hippocampal volume and activation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28743991/altered-visual-cortical-processing-in-a-mouse-model-of-mecp2-duplication-syndrome
#10
Dinghong Zhang, Bin Yu, Jing Liu, Weiqian Jiang, Taorong Xie, Ran Zhang, Dali Tong, Zilong Qiu, Haishan Yao
As an epigenetic modulator of gene expression, Methyl-CpG binding protein 2 (MeCP2) is essential for normal neurological function. Dysfunction of MeCP2 is associated with a variety of neurological disorders. MECP2 gene duplication in human causes neuropsychiatric symptoms such as mental retardation and autism. MeCP2 overexpression in mice results in neurobehavioural disorders, dendritic abnormalities, and synaptic defects. However, how gain of MeCP2 function influences cortical processing of sensory information remains unclear...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729436/regulation-of-adrenal-and-ovarian-steroidogenesis-by-mir-132
#11
Zhigang Hu, Wen-Jun Shen, Fredric B Kraemer, Salman Azhar
miR-132 is hormonally regulated in steroidogenic cells of the adrenal gland, ovary and testis. Here, we examined the potential role of miR-132 in the control of steroidogenesis. Transfection of Y1 adrenal cells with miR-132 increased mRNAs of 3β-HSD and 20α-HSD enzymes, which catalyze the sequential conversion of pregnenolone to progesterone to biologically inactive 20α-OHP. Overexpression of miR-132 reduced MeCP2 and StAR protein expression, basal progestin (progesterone and 20α-OHP) production, but enhanced their production in response to cAMP stimulation...
July 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28692032/epigenetic-silencing-of-microrna-137-enhances-asct2-expression-and-tumor-glutamine-metabolism
#12
J Dong, D Xiao, Z Zhao, P Ren, C Li, Y Hu, J Shi, H Su, L Wang, H Liu, B Li, P Gao, G Qing
Tumor cells must activate specific transporters to meet their increased glutamine metabolic demands. Relative to other glutamine transporters, the ASC family transporter 2 (ASCT2, also called SLC1A5) is profoundly elevated in a wide spectrum of human cancers to coordinate metabolic reprogramming and malignant transformation. Understanding the molecular mechanisms whereby tumor cells frequently upregulate this transporter is therefore vital to develop potential strategies for transporter-targeted therapies. Combining in-silico algorithms with systemic experimental screening, we herein identify the tumor suppressor microRNA, miR-137, as an essential regulator that targets ASCT2 and cancer cell glutamine metabolism...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28687309/reduced-axonal-diameter-of-peripheral-nerve-fibers-in-a-mouse-model-of-rett-syndrome
#13
Noha G Bahey, Kamal K E Gadalla, Rhona McGonigal, Mark E S Bailey, Julia M Edgar, Stuart R Cobb
Rett syndrome (RTT) is a neurological disorder characterized by motor and cognitive impairment, autonomic dysfunction and a loss of purposeful hand skills. In the majority of cases, typical RTT is caused by de novo mutations in the X-linked gene, MECP2. Alterations in the structure and function of neurons within the central nervous system of RTT patients and Mecp2-null mouse models are well established. In contrast, few studies have investigated the effects of MeCP2-deficiency on peripheral nerves. In this study, we conducted detailed morphometric as well as functional analysis of the sciatic nerves of symptomatic adult female Mecp2(+/-) mice...
July 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28679669/a-small-molecule-trkb-ligand-restores-hippocampal-synaptic-plasticity-and-object-location-memory-in-rett-syndrome-mice
#14
Wei Li, Alba Bellot-Saez, Mary L Phillips, Tao Yang, Frank M Longo, Lucas Pozzo-Miller
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in methyl-CpG-binding protein-2 (MECP2), a transcriptional regulator of many genes, including brain-derived neurotrophic factor (BDNF). BDNF levels are reduced in RTT autopsy brains and in multiple brain areas of Mecp2-deficient mice. Furthermore, experimental interventions that increase BDNF levels improve RTT-like phenotypes in Mecp2 mutant mice. Here, we characterized the actions of a small-molecule ligand of the BDNF receptor TrkB in hippocampal function in Mecp2 mutant mice...
July 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28674485/the-pathophysiological-role-of-microglia-in-dynamic-surveillance-phagocytosis-and-structural-remodeling-of-the-developing-cns
#15
REVIEW
Cataldo Arcuri, Carmen Mecca, Roberta Bianchi, Ileana Giambanco, Rosario Donato
In vertebrates, during an early wave of hematopoiesis in the yolk sac between embryonic day E7.0 and E9.0, cells of mesodermal leaflet addressed to macrophage lineage enter in developing central nervous system (CNS) and originate the developing native microglial cells. Depending on the species, microglial cells represent 5-20% of glial cells resident in adult brain. Here, we briefly discuss some canonical functions of the microglia, i.e., cytokine secretion and functional transition from M1 to M2 phenotype...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28671722/restoring-eeaquilibrium-rebalancing-excitation-and-inhibition-in-rett-mouse-model-neurons-with-early-endosome-antigen-1
#16
Kerry R Delaney
No abstract text is available yet for this article.
August 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28670438/neuroanatomy-in-mouse-models-of-rett-syndrome-is-related-to-the-severity-of-mecp2-mutation-and-behavioral-phenotypes
#17
Rylan Allemang-Grand, Jacob Ellegood, Leigh Spencer Noakes, Julie Ruston, Monica Justice, Brian J Nieman, Jason P Lerch
BACKGROUND: Rett syndrome (RTT) is a neurodevelopmental disorder that predominantly affects girls. The majority of RTT cases are caused by de novo mutations in methyl-CpG-binding protein 2 (MECP2), and several mouse models have been created to further understand the disorder. In the current literature, many studies have focused their analyses on the behavioral abnormalities and cellular and molecular impairments that arise from Mecp2 mutations. However, limited efforts have been placed on understanding how Mecp2 mutations disrupt the neuroanatomy and networks of the brain...
2017: Molecular Autism
https://www.readbyqxmd.com/read/28669357/mbd1-and-mecp2-expression-in-embryos-and-placentas-from-transgenic-cloned-goats
#18
Ruoxin Jia, Guomin Zhang, Yixuan Fan, Zhengrong Zhou, Yongjie Wan, Yanli Zhang, Ziyu Wang, Feng Wang
DNA methylation is an important form of epigenetic regulation in mammalian development. Methyl-CpG-binding domain protein 1 (MBD1) and methyl-CpG-binding domain protein 2 (MeCP2) are two members of the MBD subfamily of proteins that bind methylated CpG to maintain the silencing effect of DNA methylation. Given their important roles in linking DNA methylation with gene silencing, this study characterized the coordinated mRNA expression and protein localization of MBD1 and MeCP2 in embryos and placentas and aimed to analysis the effects of MBD1 and MeCP2 on transgenic cloned goats...
July 3, 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/28659760/mecp2-mediates-experience-dependent-transcriptional-upregulation-of-ryanodine-receptor-type-3
#19
Rodrigo F Torres, Cecilia Hidalgo, Bredford Kerr
Mecp2 is a DNA methylation reader that plays a critical role in experience-dependent plasticity. Increasing evidence supports a role for epigenetic modifications in activity-induced gene expression. Hence, candidate genes related to such phenomena are of great interest. Ryanodine receptors are intracellular calcium channels that contribute to hippocampal synaptic plasticity, dendritic spine remodeling, and participate in learning and memory processes. Here we exposed mice to the enriched environment (EE) paradigm, which through increased stimulation induces experience dependent-plasticity, to explore a role for methyl-cytosines, and Mecp2 in directing Ryanodine receptor 3 (Ryr3) transcriptional activity...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28655627/cpg-methylation-and-the-methyl-cpg-binding-protein-2-mecp2-are-required-for-restraining-corticotropin-releasing-hormone-crh-gene-expression
#20
Shreyas A Bhave, Rosalie M Uht
The hypothalamic-pituitary-adrenal (HPA) axis plays a critical role in mounting a stress response and maintaining homeostasis. A dysregulated HPA axis and elevated levels of CRH are associated with a number of disorders. Although extensive research has been devoted to understanding molecular events associated with stimulated CRH gene, less is known about the mechanisms that restrain CRH expression. Using a cell culture system, we report here two molecular aspects of CRH gene regulation that are required for maintenance of basal level of CRH gene expression...
October 15, 2017: Molecular and Cellular Endocrinology
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