scholarly journals ATRX tolerates activity-dependent histone H3 methyl/phos switching to maintain repetitive element silencing in neurons

2014 ◽  
Vol 112 (22) ◽  
pp. 6820-6827 ◽  
Author(s):  
Kyung-Min Noh ◽  
Ian Maze ◽  
Dan Zhao ◽  
Bin Xiang ◽  
Wendy Wenderski ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Histone Modification ◽  
Neural Development ◽  
Repetitive Element ◽  
Histone H3 ◽  
Satellite Sequences ◽  
Minor Satellite ◽  
The Central Nervous System ◽  
Activity Dependent

ATRX (the alpha thalassemia/mental retardation syndrome X-linked protein) is a member of the switch2/sucrose nonfermentable2 (SWI2/SNF2) family of chromatin-remodeling proteins and primarily functions at heterochromatic loci via its recognition of “repressive” histone modifications [e.g., histone H3 lysine 9 tri-methylation (H3K9me3)]. Despite significant roles for ATRX during normal neural development, as well as its relationship to human disease, ATRX function in the central nervous system is not well understood. Here, we describe ATRX’s ability to recognize an activity-dependent combinatorial histone modification, histone H3 lysine 9 tri-methylation/serine 10 phosphorylation (H3K9me3S10ph), in postmitotic neurons. In neurons, this “methyl/phos” switch occurs exclusively after periods of stimulation and is highly enriched at heterochromatic repeats associated with centromeres. Using a multifaceted approach, we reveal that H3K9me3S10ph-bound Atrx represses noncoding transcription of centromeric minor satellite sequences during instances of heightened activity. Our results indicate an essential interaction between ATRX and a previously uncharacterized histone modification in the central nervous system and suggest a potential role for abnormal repetitive element transcription in pathological states manifested by ATRX dysfunction.

Understanding Neuropathic Pain

CNS Spectrums ◽  
2005 ◽  
Vol 10 (4) ◽  
pp. 298-308 ◽  
Author(s):  
Walter Zieglgänsberger ◽  
Achim Berthele ◽  
Thomas R. Tölle
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neuropathic Pain ◽  
Neuronal Excitability ◽  
Traumatic Injury ◽  
Nerve Fibers ◽  
Cellular Events ◽  
Excitatory Neurotransmitters ◽  
The Central Nervous System ◽  
Activity Dependent

AbstractNeuropathic pain is defined as a chronic pain condition that occurs or persists after a primary lesion or dysfunction of the peripheral or central nervous system. Traumatic injury of peripheral nerves also increases the excitability of nociceptors in and around nerve trunks and involves components released from nerve terminals (neurogenic inflammation) and immunological and vascular components from cells resident within or recruited into the affected area. Action potentials generated in nociceptors and injured nerve fibers release excitatory neurotransmitters at their synaptic terminals such as L-glutamate and substance P and trigger cellular events in the central nervous system that extend over different time frames. Short-term alterations of neuronal excitability, reflected for example in rapid changes of neuronal discharge activity, are sensitive to conventional analgesics, and do not commonly involve alterations in activity-dependent gene expression. Novel compounds and new regimens for drug treatment to influence activity-dependent long-term changes in pain transducing and suppressive systems (pain matrix) are emerging.

Understanding cellular glycan surfaces in the central nervous system

2018 ◽  
Vol 47 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Sameera Iqbal ◽  
Mina Ghanimi Fard ◽  
Arun Everest-Dass ◽  
Nicolle H. Packer ◽  
Lindsay M. Parker
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Analytical Techniques ◽  
Detection Methods ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Enzymatic Process ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Abstract Glycosylation, the enzymatic process by which glycans are attached to proteins and lipids, is the most abundant and functionally important type of post-translational modification associated with brain development, neurodegenerative disorders, psychopathologies and brain cancers. Glycan structures are diverse and complex; however, they have been detected and targeted in the central nervous system (CNS) by various immunohistochemical detection methods using glycan-binding proteins such as anti-glycan antibodies or lectins and/or characterized with analytical techniques such as chromatography and mass spectrometry. The glycan structures on glycoproteins and glycolipids expressed in neural stem cells play key roles in neural development, biological processes and CNS maintenance, such as cell adhesion, signal transduction, molecular trafficking and differentiation. This brief review will highlight some of the important findings on differential glycan expression across stages of CNS cell differentiation and in pathological disorders and diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, amyotrophic lateral sclerosis, schizophrenia and brain cancer.

scholarly journals Tuberin levels during cellular differentiation in brain development

2021 ◽  
Author(s):  
Bashaer Abu Khatir ◽  
Gordon Omar Davis ◽  
Mariam Sameem ◽  
Rutu Patel ◽  
Jackie Fong ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Development ◽  
Cell Lines ◽  
Neural Development ◽  
Time Course ◽  
Embryonic Mouse ◽  
Organ Systems ◽  
The Central Nervous System

Tuberin is a member of a large protein complex, Tuberous Sclerosis Complex, and acts as a sensor for nutrient status regulating protein synthesis and cell cycle progression. Mutations in the Tuberin gene, TSC2, lead to the formation of tumors and developmental defects in many organ systems, including the central nervous system. Tuberin is expressed in the brain throughout development and levels of Tuberin have been found to decrease during neuronal differentiation in cell lines in vitro. Our current work investigates the levels of Tuberin at two stages of embryonic development in vivo, and we study the mRNA and protein levels during a time course using immortalized cell lines in vitro. Our results show that Tuberin levels remain stable in the olfactory bulb but decrease in the Purkinje cell layer during embryonic mouse brain development. We show here that Tuberin levels are higher when cells are cultured as neurospheres, and knockdown of Tuberin results in a reduction in the number of neurospheres. These data provide support for the hypothesis that Tuberin is an important regulator of stemness and the reduction of Tuberin levels might support functional differentiation in the central nervous system. Understanding how Tuberin expression is regulated throughout neural development is essential to fully comprehend the role of this protein in several developmental and neural pathologies.

bFGF as a possible morphogen for the anteroposterior axis of the central nervous system in Xenopus

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 3121-3130 ◽  
Author(s):  
M. Kengaku ◽  
H. Okamoto
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Anteroposterior Patterning ◽  
Anteroposterior Axis ◽  
Spemann's Organizer ◽  
The Central Nervous System ◽  
Dorsal Ectoderm ◽  
Higher Doses

Vertebrate neural development is initiated during gastrulation by the inductive action of the dorsal mesoderm (Spemann's organizer in amphibians) on neighbouring ectoderm, which eventually gives rise to the central nervous system from forebrain to spinal cord. Here we present evidence that bFGF can mimic the organizer action by inducing Xenopus ectoderm cells in culture to express four position-specific neural markers (XeNK-2, En-2, XIHbox1 and XIHbox6) along the anteroposterior axis. bFGF also induced the expression of a general neural marker NCAM but not the expression of immediate-early mesoderm markers (goosecoid, noggin, Xbra and Xwnt-8), suggesting that bFGF directly neuralized ectoderm cells without forming mesodermal cells. The bFGF dose required to induce the position-specific markers was correlated with the anteroposterior location of their expression in vivo, with lower doses eliciting more anterior markers and higher doses more posterior markers. These data indicate that bFGF or its homologue is a promising candidate for a neural morphogen for anteroposterior patterning in Xenopus. Further, we showed that the ability of ectoderm cells to express the anterior markers in response to bFGF was lost by mid-gastrula, before the organizer mesoderm completely underlies the anterior dorsal ectoderm. Thus, an endogenous FGF-like molecule released from the involuting organizer may initiate the formation of the anteroposterior axis of the central nervous system during the early stages of gastrulation by forming a concentration gradient within the plane of dorsal ectoderm.

scholarly journals Social Experience-Dependent Myelination: An Implication for Psychiatric Disorders

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Michihiro Toritsuka ◽  
Manabu Makinodan ◽  
Toshifumi Kishimoto
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Conduction Velocity ◽  
Neuronal Activity ◽  
Social Experience ◽  
Multiple Factors ◽  
The Central Nervous System ◽  
Extracellular Molecules ◽  
Activity Dependent

Myelination is one of the strategies to promote the conduction velocity of axons in order to adjust to evolving environment in vertebrates. It has been shown that myelin formation depends on genetic programing and experience, including multiple factors, intracellular and extracellular molecules, and neuronal activities. Recently, accumulating studies have shown that myelination in the central nervous system changes more dynamically in response to neuronal activities and experience than expected. Among experiences, social experience-dependent myelination draws attention as one of the critical pathobiologies of psychiatric disorders. In this review, we summarize the mechanisms of neuronal activity-dependent and social experience-dependent myelination and discuss the contribution of social experience-dependent myelination to the pathology of psychiatric disorders.

scholarly journals Multiple Functions of the Dmrt Genes in the Development of the Central Nervous System

2021 ◽  
Vol 15 ◽  
Author(s):  
Takako Kikkawa ◽  
Noriko Osumi
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Sexual Development ◽  
Embryonic Brain ◽  
Multiple Functions ◽  
The Central Nervous System ◽  
Brain And Spinal Cord ◽  
Brain Patterning

The Dmrt genes encode the transcription factor containing the DM (doublesex and mab-3) domain, an intertwined zinc finger-like DNA binding module. While Dmrt genes are mainly involved in the sexual development of various species, recent studies have revealed that Dmrt genes, which belong to the DmrtA subfamily, are differentially expressed in the embryonic brain and spinal cord and are essential for the development of the central nervous system. Herein, we summarize recent studies that reveal the multiple functions of the Dmrt genes in various aspects of vertebrate neural development, including brain patterning, neurogenesis, and the specification of neurons.

scholarly journals Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity

2020 ◽  
Vol 21 (4) ◽  
pp. 1538 ◽  
Author(s):  
Luca Franchini ◽  
Nicolò Carrano ◽  
Monica Di Luca ◽  
Fabrizio Gardoni
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Synaptic Plasticity ◽  
Receptor Subtypes ◽  
Interacting Proteins ◽  
Regulatory Subunits ◽  
Different Types ◽  
The Central Nervous System ◽  
Nmdar Subunit ◽  
Activity Dependent

N-Methyl-d-Aspartate Receptors (NMDARs) are ionotropic glutamate-gated receptors. NMDARs are tetramers composed by several homologous subunits of GluN1-, GluN2-, or GluN3-type, leading to the existence in the central nervous system of a high variety of receptor subtypes with different pharmacological and signaling properties. NMDAR subunit composition is strictly regulated during development and by activity-dependent synaptic plasticity. Given the differences between GluN2 regulatory subunits of NMDAR in several functions, here we will focus on the synaptic pool of NMDARs containing the GluN2A subunit, addressing its role in both physiology and pathological synaptic plasticity as well as the contribution in these events of different types of GluN2A-interacting proteins.

scholarly journals THE ROLE OF THROMBIN IN CENTRAL NERVOUS SYSTEM ACTIVITY AND STROKE

2018 ◽  
Vol 91 (4) ◽  
pp. 368-371 ◽  
Author(s):  
Ancuța-Maria Pleșeru ◽  
Romeo Gabriel Mihailă
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Thrombin Inhibitors ◽  
Cerebral Stroke ◽  
Mesh Terms ◽  
Central Nervous System Activity ◽  
Key Factor ◽  
The Central Nervous System

Background. Thrombin is a key factor of hemostasis, mediating the conversion of fibrinogen into fibrin. Along with prothrombin, of which thrombin is the active derivative, it has been found locally expressed in the central nervous system. This article aims to describe the role of thrombin in the normal functioning of the central nervous system and stroke.Methods. In this mini-review, the specialized databases Medscape, PubMed, and Web of Science, from the years 2003-2018, were used to find relevant documents by using MeSH terms: ”thrombin” and ”stroke”.Results. Prothrombin and thrombin influence neural development, protection and regeneration, thrombin being a relatively strong regulating factor of brain function. However, high levels of thrombin are detrimental to neuronal health, and cause atherosclerotic plaque development and instability - a leading cause of cerebral infarction. In stroke, thrombin promotes direct cellular toxicity, vascular disruption, oxidative stress and inflammatory response. There is a direct correlation between thrombin activity in the affected brain hemisphere and the infarction volume. Direct acting thrombin inhibitors, like dabigatran, significantly decrease the risk of ischemic stroke.Conclusion. Further studies on the correlation between thrombin levels, generation and activity and the risk and recurrence of ischemic cerebral stroke should give new insight on this association, resulting in an optimized practical therapeutic approach.

scholarly journals Myelin in the Central Nervous System: Structure, Function, and Pathology

2019 ◽  
Vol 99 (3) ◽  
pp. 1381-1431 ◽  
Author(s):  
Christine Stadelmann ◽  
Sebastian Timmler ◽  
Alonso Barrantes-Freer ◽  
Mikael Simons
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nerve Conduction ◽  
Active Role ◽  
Acute Disseminated Encephalomyelitis ◽  
System Structure ◽  
The Central Nervous System ◽  
Relationship Of ◽  
Activity Dependent

Oligodendrocytes generate multiple layers of myelin membrane around axons of the central nervous system to enable fast and efficient nerve conduction. Until recently, saltatory nerve conduction was considered the only purpose of myelin, but it is now clear that myelin has more functions. In fact, myelinating oligodendrocytes are embedded in a vast network of interconnected glial and neuronal cells, and increasing evidence supports an active role of oligodendrocytes within this assembly, for example, by providing metabolic support to neurons, by regulating ion and water homeostasis, and by adapting to activity-dependent neuronal signals. The molecular complexity governing these interactions requires an in-depth molecular understanding of how oligodendrocytes and axons interact and how they generate, maintain, and remodel their myelin sheaths. This review deals with the biology of myelin, the expanded relationship of myelin with its underlying axons and the neighboring cells, and its disturbances in various diseases such as multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica spectrum disorders. Furthermore, we will highlight how specific interactions between astrocytes, oligodendrocytes, and microglia contribute to demyelination in hereditary white matter pathologies.

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