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Mef2a neuron

Stefania Trazzi, Claudia Fuchs, Rocchina Viggiano, Marianna De Franceschi, Emanuele Valli, Paulina Jedynak, Finn K Hansen, Giovanni Perini, Roberto Rimondini, Thomas Kurz, Renata Bartesaghi, Elisabetta Ciani
Cyclin-dependent kinase-like 5 (CDKL5) is a Ser/Thr protein kinase predominantly expressed in the brain. Mutations of the CDKL5 gene lead to CDKL5 disorder, a neurodevelopmental pathology that shares several features with Rett Syndrome and is characterized by severe intellectual disability. The phosphorylation targets of CDKL5 are largely unknown, which hampers the discovery of therapeutic strategies for improving the neurological phenotype due to CDKL5 mutations. Here, we show that the histone deacetylase 4 (HDAC4) is a direct phosphorylation target of CDKL5 and that CDKL5-dependent phosphorylation promotes HDAC4 cytoplasmic retention...
July 27, 2016: Human Molecular Genetics
Elena Neumann, Timo Brandenburger, Sonia Santana-Varela, René Deenen, Karl Köhrer, Inge Bauer, Henning Hermanns, John N Wood, Jing Zhao, Robert Werdehausen
BACKGROUND: MicroRNAs (miRNAs) regulate gene expression in physiological as well as in pathological processes, including chronic pain. Whether deletion of a gene can affect expression of the miRNAs that associate with the deleted gene mRNA remains elusive. We investigated the effects of brain-derived neurotrophic factor (Bdnf) gene deletion on the expression of miR-1 in dorsal root ganglion (DRG) neurons and its pain-associated downstream targets heat shock protein 60 (Hsp60) and connexin 43 (Cx43) in tamoxifen-inducible conditional knockout mice, Bdnf(fl/fl); Advillin-CreER(T2) (Bdnf cKO)...
September 2016: Molecular and Cellular Neurosciences
Qi Ma, Francesca Telese
The transcription factors of the myocyte enhancer factor 2 family (MEF2 A-D) are highly expressed in the brain and play a key role in neuronal survival/apoptosis, differentiation and synaptic plasticity. However, the precise genome-wide mapping of different members of the family has not yet been fully elucidated. Here, we report the comparative analysis of MEF2A and MEF2C genome-wide mapping in mouse cortical neurons by ChIP-seq, a powerful approach to elucidate the genomic functions of transcription factors and to identify their transcriptional targets...
November 2015: Communicative & Integrative Biology
Yunyi Huang, Xuling Wu, Jing Guo, Jinxian Yuan
Myocyte-specific enhancer binding factor 2A (MEF2A) is a multifunctional nuclear protein that regulates synaptogenesis, dendritic morphogenesis, and neuronal survival. This study aimed to investigate the expression pattern of MEF2A in epileptogenic processes. MEF2A expression was detected in 20 temporal neocortex tissue samples from patients with temporal lobe epilepsy (TLE) and 20 samples from trauma patients without epilepsy by real-time quantitative polymerase chain reaction, immunohistochemistry, double-label immunofluorescent staining, and western blot analysis...
September 2016: International Journal of Neuroscience
Sarah E Latchney, Yindi Jiang, David P Petrik, Amelia J Eisch, Jenny Hsieh
Myocyte enhancer factor (Mef)-2 transcription factors are implicated in activity-dependent neuronal processes during development, but the role of MEF2 in neural stem/progenitor cells (NSPCs) in the adult brain is unknown. We used a transgenic mouse in which Mef2a, -c, and -d were inducibly deleted in adult nestin-expressing NSPCs and their progeny. Recombined cells in the hippocampal granule cell layer were visualized and quantified by yellow fluorescent protein (YFP) expression. In control mice, postmitotic neurons expressed Mef2a, -c, and -d, whereas type 1 stem cells and proliferating progenitors did not...
December 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Li Zhang, Yang Sun, Mingjian Fei, Cheng Tan, Jing Wu, Jie Zheng, Jiqing Tang, Wei Sun, Zhaoliang Lv, Jiandong Bao, Qiang Xu, Huixin Yu
Oxidative stress has been implicated in both normal aging and various neurodegenerative disorders and it may be a major cause of neuronal death. Chaperone-mediated autophagy (CMA) targets selective cytoplasmic proteins for degradation by lysosomes and protects neurons against various extracellular stimuli including oxidative stress. MEF2A (myocyte enhancer factor 2A), a key transcription factor, protects primary neurons from oxidative stress-induced cell damage. However, the precise mechanisms of how the protein stability and the transcriptional activity of MEF2A are regulated under oxidative stress remain unknown...
June 2014: Autophagy
Denise Cazzato, Emma Assi, Claudia Moscheni, Silvia Brunelli, Clara De Palma, Davide Cervia, Cristiana Perrotta, Emilio Clementi
The muscle-specific variant of neuronal nitric oxide (NO) synthase (NOS-I), is developmentally regulated in mouse suggesting a role of NO during myogenesis. In chick embryo, a good model of development, we found that the expression of NOS-I is up-regulated, but only in the early phase of development. Through a pharmacological intervention in ovo we found that NO signalling plays a relevant role during embryonic development. The inhibition of NOS-I decreased the growth of embryo, in particular of muscle tissue, while the restoring of physiological NO levels, via administration of a NO donor, reversed this effect...
January 15, 2014: Experimental Cell Research
Thomas A Lanz, Edward Guilmette, Mark M Gosink, James E Fischer, Lawrence W Fitzgerald, Diane T Stephenson, Mathew T Pletcher
BACKGROUND: Austism spectrum disorder (ASD) is a heterogeneous behavioral disorder or condition characterized by severe impairment of social engagement and the presence of repetitive activities. The molecular etiology of ASD is still largely unknown despite a strong genetic component. Part of the difficulty in turning genetics into disease mechanisms and potentially new therapeutics is the sheer number and diversity of the genes that have been associated with ASD and ASD symptoms. The goal of this work is to use shRNA-generated models of genetic defects proposed as causative for ASD to identify the common pathways that might explain how they produce a core clinical disability...
2013: Molecular Autism
Wen-Yuan Wang, Yan Luo, Li-Jie Jia, Shuang-Fei Hu, Xiao-Kan Lou, She-Liang Shen, Han Lu, Hong-Hai Zhang, Rui Yang, Hua Wang, Zheng-Wen Ma, Qing-Sheng Xue, Bu-Wei Yu
Aberrant CDK5 activity is implicated in a number of neurodegenerative disorders. Isoflurane exposure leads to neuronal apoptosis, and subsequent learning and memory defects in the developing brain. The present study was designed to examine whether and how CDK5 activity plays a role in developmental isoflurane neurotoxicity. Rat pups and hippocampal neuronal cultures were exposed to 1.5% isoflurane for 4 h. The protein and mRNA levels of CDK5, p35 and p25 were detected by western blot and QReal-Time PCR. CDK5 activity was evaluated in vitro using Histone H1 as a substrate...
February 2014: Neuropharmacology
Tomoko Yamada, Yue Yang, Ju Huang, Giovanni Coppola, Daniel H Geschwind, Azad Bonni
Presynaptic differentiation of axons plays a fundamental role in the establishment of neuronal connectivity. However, the mechanisms that govern presynaptic differentiation in the brain remain largely to be elucidated. We report that knockdown of the transcription factor MEF2A in primary neurons and importantly in the rat cerebellar cortex in vivo robustly increases the density of orphan presynaptic sites. Remarkably, the sumoylated transcriptional repressor form of MEF2A drives the suppression of orphan presynaptic sites...
March 13, 2013: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Simon Xuan Chen, Angus Cherry, Parisa Karimi Tari, Kaspar Podgorski, Yue Kay Kali Kwong, Kurt Haas
Natural sensory input shapes both structure and function of developing neurons, but how early experience-driven morphological and physiological plasticity are interrelated remains unclear. Using rapid time-lapse two-photon calcium imaging of network activity and single-neuron growth within the unanesthetized developing brain, we demonstrate that visual stimulation induces coordinated changes to neuronal responses and dendritogenesis. Further, we identify the transcription factor MEF2A/2D as a major regulator of neuronal response to plasticity-inducing stimuli directing both structural and functional changes...
September 28, 2012: Cell
Michelle R Lyons, Charlotte M Schwarz, Anne E West
Transcription of the gene encoding brain-derived neurotropic factor (BDNF) is induced in response to a wide variety of extracellular stimuli via the activation of a complex array of transcription factors. However, to what degree individual transcription factors confer specificity upon the regulation of Bdnf is poorly understood. Previous studies have shown that members of the myocyte enhancer factor 2 (MEF2) transcription factor family bind a regulatory element upstream of Bdnf promoter I and associate with an unknown binding site in Bdnf promoter IV...
September 12, 2012: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Hua She, Qian Yang, Zixu Mao
The myocyte enhancer factor 2A-D (MEF2) proteins are members of the MCM1-agamous-deficiens-serum response factor family of transcription factors. Various MEF2 isoform proteins are enriched in neurons and exhibit distinct patterns of expression in different regions of the brain. In neurons, MEF2 functions as a converging factor to regulate many neuronal functions including survival. MEF2 activities are tightly controlled in neurons in response to stress. Whether stress signal may differentially regulate MEF2s remains largely unknown...
September 2012: Journal of Neurochemistry
David Petrik, Yindi Jiang, Shari G Birnbaum, Craig M Powell, Mi-Sung Kim, Jenny Hsieh, Amelia J Eisch
Adult neurogenesis occurs throughout life in the mammalian hippocampus and is essential for memory and mood control. There is significant interest in identifying ways to promote neurogenesis and ensure maintenance of these hippocampal functions. Previous work with a synthetic small molecule, isoxazole 9 (Isx-9), highlighted its neuronal-differentiating properties in vitro. However, the ability of Isx-9 to drive neurogenesis in vivo or improve hippocampal function was unknown. Here we show that Isx-9 promotes neurogenesis in vivo, enhancing the proliferation and differentiation of hippocampal subgranular zone (SGZ) neuroblasts, and the dendritic arborization of adult-generated dentate gyrus neurons...
August 2012: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
M Waseem Akhtar, Mi-Sung Kim, Megumi Adachi, Michael J Morris, Xiaoxia Qi, James A Richardson, Rhonda Bassel-Duby, Eric N Olson, Ege T Kavalali, Lisa M Monteggia
MEF2 (A-D) transcription factors govern development, differentiation and maintenance of various cell types including neurons. The role of MEF2 isoforms in the brain has been studied using in vitro manipulations with only MEF2C examined in vivo. In order to understand specific as well as redundant roles of the MEF2 isoforms, we generated brain-specific deletion of MEF2A and found that Mef2aKO mice show normal behavior in a range of paradigms including learning and memory. We next generated Mef2a and Mef2d brain-specific double KO (Mef2a/dDKO) mice and observed deficits in motor coordination and enhanced hippocampal short-term synaptic plasticity, however there were no alterations in learning and memory, Schaffer collateral pathway long-term potentiation, or the number of dendritic spines...
2012: PloS One
Jiali Li, Jianmin Chen, Christopher L Ricupero, Ronald P Hart, Melanie S Schwartz, Alexander Kusnecov, Karl Herrup
Ataxia telangiectasia is a neurodegenerative disease caused by mutation of the Atm gene. Here we report that ataxia telangiectasia mutated (ATM) deficiency causes nuclear accumulation of histone deacetylase 4 (HDAC4) in neurons and promotes neurodegeneration. Nuclear HDAC4 binds to chromatin, as well as to myocyte enhancer factor 2A (MEF2A) and cAMP-responsive element binding protein (CREB), leading to histone deacetylation and altered neuronal gene expression. Blocking either HDAC4 activity or its nuclear accumulation blunts these neurodegenerative changes and rescues several behavioral abnormalities of ATM-deficient mice...
May 2012: Nature Medicine
Charles Plessy, Giovanni Pascarella, Nicolas Bertin, Altuna Akalin, Claudia Carrieri, Anne Vassalli, Dejan Lazarevic, Jessica Severin, Christina Vlachouli, Roberto Simone, Geoffrey J Faulkner, Jun Kawai, Carsten O Daub, Silvia Zucchelli, Yoshihide Hayashizaki, Peter Mombaerts, Boris Lenhard, Stefano Gustincich, Piero Carninci
Odorous chemicals are detected by the mouse main olfactory epithelium (MOE) by about 1100 types of olfactory receptors (OR) expressed by olfactory sensory neurons (OSNs). Each mature OSN is thought to express only one allele of a single OR gene. Major impediments to understand the transcriptional control of OR gene expression are the lack of a proper characterization of OR transcription start sites (TSSs) and promoters, and of regulatory transcripts at OR loci. We have applied the nanoCAGE technology to profile the transcriptome and the active promoters in the MOE...
March 2012: Genome Research
Hortensia Sanchez-Calderon, Lourdes Rodriguez-de la Rosa, Marta Milo, Jose G Pichel, Matthew Holley, Isabel Varela-Nieto
BACKGROUND: Insulin-like growth factor-I (IGF-I) provides pivotal cell survival and differentiation signals during inner ear development throughout evolution. Homozygous mutations of human IGF1 cause syndromic sensorineural deafness, decreased intrauterine and postnatal growth rates, and mental retardation. In the mouse, deficits in IGF-I result in profound hearing loss associated with reduced survival, differentiation and maturation of auditory neurons. Nevertheless, little is known about the molecular basis of IGF-I activity in hearing and deafness...
2010: PloS One
M Diana Neely, Elizabeth M Robert, Anthony J Baucum, Roger J Colbran, E Chris Muly, Ariel Y Deutch
The transcription factor myocyte enhancer factor 2 (MEF2) is expressed throughout the central nervous system, where four MEF2 isoforms play important roles in neuronal survival and differentiation and in synapse formation and maintenance. It is therefore somewhat surprising that there is a lack of detailed information on the localization of MEF2 isoforms in the mammalian brain. We have analyzed the regional, cellular, and subcellular expression of MEF2A and MEF2D in the rodent brain. These two MEF2 isoforms were co-expressed in virtually all neurons in the cortex and the striatum, but were not detected in astrocytes...
June 5, 2009: Brain Research
Julia M Gohlke, Olivier Armant, Frederick M Parham, Marjolein V Smith, Celine Zimmer, Diogo S Castro, Laurent Nguyen, Joel S Parker, Gerard Gradwohl, Christopher J Portier, François Guillemot
BACKGROUND: The proneural proteins Mash1 and Ngn2 are key cell autonomous regulators of neurogenesis in the mammalian central nervous system, yet little is known about the molecular pathways regulated by these transcription factors. RESULTS: Here we identify the downstream effectors of proneural genes in the telencephalon using a genomic approach to analyze the transcriptome of mice that are either lacking or overexpressing proneural genes. Novel targets of Ngn2 and/or Mash1 were identified, such as members of the Notch and Wnt pathways, and proteins involved in adhesion and signal transduction...
2008: BMC Biology
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