Download or read book Gene Regulation During Central Nervous System Development and Post injury Regeneration written by Ying Li and published by . This book was released on 2016 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: Central nervous system (CNS) development and post-injury neurogenesis require accurate coordination of neural stem cell proliferation, progenitor cell differentiation, neuron, glia migration and maturation, and synapse formation between axons and dendrites. Such systems with high complexity require strict temporal and spatial control via several levels of regulation, in which the transcription regulation is one of the most critical steps. The developmental and injury-repair process involves over 18,000 genes, for majority of which the molecular mechanism governing their transcription remains largely unknown. In an attempt to address this question, four projects were conducted focusing on two levels of transcription regulation: i.e., chromatin modification, and the interaction of cis-acting regulatory sequences with trans-acting protein factors. Computational methods were adopted to analyze the sequences of the cis-elements and iii make predictions for their interacting transcription factors (TFs). The functional roles of these cis- and trans-elements were further determined in vivo and in vitro. The following findings are presented: 1) the function of DNA topoisomerase II beta (Top2b) in proper laminar formation and cell survival during retinal development; 2) the development of computational method for identifying gene regulatory networks involving enhancers and master TFs that are important in retinal cell differentiation; 3) the mechanism of Notch1 regulation in neural stem/progenitor cells via the interaction between Nkx6.1 and a CNS specific enhancer CR2 during the development of the spinal cord interneurons; and 4) the role of CR2 in aNSC activation after injury. Findings from this dissertation provide new insights into the molecular mechanisms underlying transcription regulation during CNS development and post-injury neurogenesis. They can also serve as a basis for future development of gene therapies and regenerative medicine for neurological disorders including spinal cord injury.
Download or read book Immediate Early Genes in the Central Nervous System written by T.R. Tölle and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Immediate-early genes are believed to be involved in the neuron's ability to con vert short-term synaptic stimulation into long-lasting responses and thus contribute to the adaptive alterations involved in neuronal plasticity. Cellular immediate-early genes share a close structural homology with some viral oncogenes. Recent advances in cellular biology have identified the activation and deactivation of immediate-early genes as molecular mechanisms to control regulated and deregulated growth, cellular differentiation and development. In this view immediate-early genes may function as third messengers in a stimulus transcription cascade transferring extracellular information into changes in target gene transcription, thereby changing the phenotype of neurons. Immediate-Early Genes in the Central Nervous System provides a comprehensive up-to-date overview of current methodology in the research of immediate-early genes and includes a wide range of neurobiological topics, such as regeneration, memory formation, epilepsia and nociception. The contributors to this book have been selected from among the leading experts in their field of research. T.R. TOLLE J. SCHADRACK W. ZIEGLGANSBERGER Contents Immediate-early genes -how immmediate and why early? G./. Evan .............................................. . Immediate-early gene activation as a window on mechanism in the nervous system S.P. Hunt, L.A. McNaughton, R. Jenkins, and W. Wisden. . . . . . . . . .. . . . 18 of immediate-early genes during Differential expression synaptic plasticity, seizures and brain injury suggests specific functions for these molecules in brain neurons M. Dragunow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . 35 . . . . . . . . . .
Download or read book Gene Expression in the Central Nervous System written by A.C.H. Yu and published by Elsevier. This book was released on 1995-08-01 with total page 359 pages. Available in PDF, EPUB and Kindle. Book excerpt: Gene expression is an active ongoing process that maintains a functional CNS, as proteins are being made on a continual basis. Processes such as learning and memory, nerve cell repair and regeneration and its response to stress are critically dependent on gene expression. This volume highlights the role of gene expression in normal CNS function, and presents many research methods at the cutting edge of neuroscience, which will provide insight into therapeutic approaches through which the control of gene expression may be used in the treatment of many nervous system diseases.
Download or read book Regulation of Gene Expression in the Nervous System written by Anna Maria Giuffrida Stella and published by . This book was released on 1990-07-19 with total page 504 pages. Available in PDF, EPUB and Kindle. Book excerpt: Offers an up-to-date account of the latest research findings concerned with the regulatory mechanisms of gene expression in neuronal and glial cells under different conditions. The book explores the cellular and neurobiological aspects of important phenomena of the nervous system and its role in health, disease and injury. Contributions from prominent scientists in the field address a variety of specific topics concerned with gene expression in the nervous system--from growth, hormonal and trophic factors to neural tissue reactions in injury or aging.
Download or read book From Development to Degeneration and Regeneration of the Nervous System written by Charles E. Ribak PhD and published by Oxford University Press. This book was released on 2008-12-16 with total page 404 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides current information about the three areas mentioned in the title: Neuronal Migration and Development, Degenerative Brain Diseases, and Neural Plasticity and Regeneration. The chapters about brain development examine the cellular and molecular mechanisms by which neurons are generated from the ventricular zone in the forebrain and migrate to their destinations in the cerebral cortext. This description of cortical development also includes a discussions of the Cajal-Retzius cell. Another chapter provides insight about the development of another forebrain region, the hypothalamus. The remaining chapters of this section examine the clinical relevance of brain development in certain disease states in humans: neural tube defects and the normal and abnormal development of human electroencephalographic recordings during the first year of age. The second section on degenerative disorders of the brain begins wtih details about the dopaminergic neurons in the substantia niger and their loss in Parkinson's disease. Two subsequent chapters describe changes in brain aging, including changes in the numbers of myelinated axons. Other chapters in this section describe important cellular and molecular changes found in Alzheimer's disease and human epilepsy. Together, these chapters summarize much of our current knowledge about the major molecular and cellular changes found in several degenerative diseases of the brain. The last section addresses the issues of brain plasticity and regeneration in the adult brain and begins with a chapter on how the brain's own stem cells provide newly generated neurons to the hippocampal dentate gyrus and how these neurons become integrated into neural circuitry. The following two chapters examine some of the neuroplastic changes that take place in motor and sensory cortices of awake behaving primates. The concluding two chapters address the issue of regeneration in the injured spinal cord and the factors that may contribute to its success.
Download or read book Degeneration and Regeneration in the Nervous System written by Norman Saunders and published by CRC Press. This book was released on 2000-01-13 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: Degeneration and Regeneration in the Nervous System brings together an international team of contributors to produce a series of critical reviews appraising key papers in the field. The pace of research on brain and spinal cord injury quickened considerably in the last ten years and there is much that is new and important that is covered in this bo
Download or read book Transcriptional and Epigenetic Regulation of Axon Regeneration written by Marcus Mahar and published by . This book was released on 2019 with total page 146 pages. Available in PDF, EPUB and Kindle. Book excerpt: The mammalian nervous system is a highly intricate network consisting of over a hundred billion specialized cells called neurons. One unique characteristic of neurons is their highly polarized morphology; unlike other cells, neurons project long axonal extensions. These structures allow them to connect and communicate with not only other neurons, but also various cell types in the body and give rise to all motor, sensory, and higher order function. Because axons can extend up to three feet, they are also vulnerable to injury from sources such as traumatic brain and spinal cord injuries, stroke, or neurodegenerative diseases. Indeed, patients who have experienced these injuries often suffer debilitating, irreversible loss of function. Interestingly, whereas neurons which reside in the central nervous system are incapable of regenerating after axon injury, neurons of the peripheral nervous system activate a robust pro-regenerative response capable of promoting long distance regeneration and functional recovery. The molecular mechanisms which underlie this pro-regenerative response may provide key insights into how a pro-regenerative response could be stimulated in injured central nervous system neurons. A comprehensive overview of the known molecular mechanisms involved in this response is reviewed in Chapter 1.As mammals age, the synaptic connections between neurons mature. Following axon injury in peripheral nervous system neurons, the genes involved in synaptic function are turned off and genes required for inducing axon growth are activated. These widespread epigenetic and transcriptional changes require a coordinated effort of epigenetic and transcriptional regulators including epigenetic modifiers, transcription factors, and microRNAs. In Chapter 2, we demonstrated that these changes are, in part, a result of the rapid downregulation of microRNA-9 which occurs following axon injury. At baseline in adult peripheral nervous system neurons, microRNA-9 is highly expressed and actively represses various genes including REST and UHRF1. When microRNA-9 expression decreases following injury, both REST and UHRF1 increase with UHRF1also repressing REST and restricting REST expression to a tight temporal window. During this time, REST binds to and represses various genes involved in synaptic function such as ion channels; a process necessary for peripheral nervous system regeneration. This complete published work can be found in Chapter 2.In coordination with epigenetic modifiers such as UHRF1, various transcription factors are activated following axon injury and promote the expression of pro-growth genes. Various studies have worked to identify the transcription factors involved in this process as exogenous overexpression of transcription factors has been shown to confer specific phenotypes of interest, such as the conversion of one cell type to another, when the correct combination of transcription factors is manipulated. To further this work, in Chapter 3 I used bioinformatics analysis to identify 27 transcription factors putatively involved in the establishment of the pro-regenerative response. Using two complimentary in vitro screens, determined which transcription factors were both necessary for peripheral nervous system axon regeneration and sufficient to drive central nervous system axon regeneration. By pairing these results with network-based bioinformatics analysis, we identified Creb1 as a transcription factor which sits atop the pro-regenerative gene regulatory network. Follow-up studies in which we overexpressed Creb1during optic nerve regeneration demonstrated Creb1 is sufficient to promote central nervous system axon regeneration in vivo. This work provides exciting new insight into the various transcription factors regulating this response as well as their putative genetic relationships.
Download or read book Axonal Regeneration in the Central Nervous System written by Nicholas A Ingoglia and published by CRC Press. This book was released on 2000-09-29 with total page 736 pages. Available in PDF, EPUB and Kindle. Book excerpt: Summarizing a review of research into factors that regulate, stimulate, and prevent regeneration in the central nervous system (CNS), this comprehensive reference progresses further into answering and resolving neuron capacity for axon regeneration in the mammalian CNS. Axonal Regeneration in the Central Nervous System analyzes axonal regeneration, reinnervation, and functional recovery in lower vertebrates examines the correlation between developmental age and the ability to regenerate considers mammalian neuron responses at the cell body, site of injury, and in the distal nerve, including apoptic cell death, and inflammatory and glial responses to injury reviews genomic responses to axotomy with a comparative description of transcribed genes from successfully regenerating neurons and neurons incapable of regrowth discusses how growing axons may induce the expression of genes in glia/Schwann cells following axotomy and regeneration describes the use of gene therapy to deliver trophic and survival factors to injured neurons explores the hospitable environments of the peripheral nerve, olfactory ensheathing cells, and fetal cell transplants for regeneration discusses results from applications of fetal CNS tissue to human spinal cord injuries and much more!
Download or read book Transcriptional Regulation in the Peripheral Nervous System and the Role of Stat3 in Axon Regeneration written by Robin Patrick Smith and published by . This book was released on 2008 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Several factors contribute to the failure of the central nervous system (CNS) to regenerate after injury. These include inhibition of axonal growth by myelin and glial scar associated molecules, as well as the intrinsic inability of adult CNS neurons to grow long axons in environments that are permissive for younger neurons. Neurons in the peripheral nervous system (PNS) display a much higher capacity to regenerate after injury than CNS neurons, as shown by conditioning lesion experiments and by microtransplantation of dorsal root ganglia neurons into CNS white matter tracts. Our central hypothesis is that neurons of the PNS express specific regeneration associated genes that mediate their enhanced growth response after injury. We have employed a combination of subtractive hybridization, microarray comparison and promoter analysis to probe for genes specific to neurons of the dorsal root ganglia (DRG), using cerebellar granule neurons (CGN) as a reference. We have identified over a thousand different genes, many of whose products form interaction networks and signaling pathways. Moreover, we have identified several dozen transcription factors that may play a role in establishing DRG neuron identity and shape their responses after injury. One of these transcription factors is Signal Transducer and Activator of Transcription 3 (STAT3), previously known to be upregulated in the PNS after a conditioning lesion but not known to be specific to the PNS. Using a real time PCR and immunochemical approaches we have shown that STAT3 is constitutively expressed and selectively active in DRG neurons both in culture and in vivo. We show that the overexpression of wild type STAT3 in cerebellar granule neurons leads to the formation of supernumerary neurites, whereas the overexpression of constitutively active STAT3-C leads to a 20% increase in total neurite outgrowth. It is hoped that the genetic delivery of STAT3-C, potentially combined with co-activators of transcription, will improve functional regeneration of CNS axons in vivo.
Download or read book Central Nervous System Development and Injury Characterization of Cytoskeletal Gene Expression in Neurons and Glia written by Susanne Arlene Mikucki and published by . This book was released on 1991 with total page 486 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Indwelling Neural Implants written by William M. Reichert and published by CRC Press. This book was released on 2007-12-17 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite enormous advances made in the development of external effector prosthetics over the last quarter century, significant questions remain, especially those concerning signal degradation that occurs with chronically implanted neuroelectrodes. Offering contributions from pioneering researchers in neuroprosthetics and tissue repair, Indwel
Download or read book Investigating Molecular Mechanisms of Neuronal Regeneration written by Alison Margaret Blain and published by . This book was released on 2009 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: Injury to the peripheral nervous system (PNS) stimulates a finely regulated regenerative response that generally leads to some recovery of function. In contrast, the response to injury in the adult mammalian central nervous system (CNS) is abortive and adult CNS neurons do not normally regenerate. We used a microarray approach to identify putative regeneration-associated changes in gene expression in the L4 dorsal root ganglion (DRG) in rat models of PNS and CNS injury. Our models included crush injury to both branches of the bifurcating axon of sensory neurons with cell bodies in the DRG (DRGNs). Injury to the peripheral branch at the level of the spinal nerve (SN) results in axonal regeneration and reinnervation. Crush injury of the central branch in the dorsal root (DR) results in active regeneration up to the point of CNS entry at the DR entry zone (DREZ) and subsequent arrest of further growth, while transection injury within the CNS at the level of the dorsal columns (DC) results in abortive and unsuccessful regeneration attempts. These DRGN injury models therefore allowed us to compare the gene expression programmes elicited during active, arrested and abortive regeneration. Following a pilot microarray experiment to optimize experimental parameters and tract tracing and electrophysiological experiments to confirm time points for harvest of DRGs after DR and SN injury, respectively, male Sprague-Dawley rats underwent an L4 SN crush, an L4 DR crush or a bilateral DC transection at the L3/L4 spinal segment boundary. L4 DRGs were collected at 2 weeks (active regeneration) and 6 weeks (arrested regeneration) after DR crush. DRGs were harvested at 6 weeks after SN crush and 2 weeks after DC transection. DRGs harvested from naïve rats served as a control group. Microarray analysis (Affymetrix Rat genome 230 2.0 array) identified several hundred genes showing differential expression (5% FDR) in comparisons of regenerating with non-regenerating conditions. Selected genes were chosen for validation by qRT-PCR. These genes could represent putative regeneration-associated genes and may suggest novel therapeutic interventions to encourage regeneration of the spinal cord following injury. Additionally, we have identified genes upregulated in the DR active regeneration state relative to DR arrested state, which have relevance to root avulsion injury and may provide insight into the mechanisms that prevent regeneration of DR axons through the DREZ to re-enter the spinal cord. We also present evidence that a transcriptional programme consistent with regeneration is mounted within the DRG following DC transection. This lends support to the idea that CNS neurons have intrinsic regenerative capability and that manipulations of the CNS environment may be sufficient to permit regeneration of CNS axons.
Download or read book Identification of Novel Genes Critical for CNS Regeneration in L Stagnalis written by Mila Aleksic and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Identification of Regulatory Factors that Control Nervous System Form Function and Regeneration in the Planarian Schmidtea Mediterranea written by Martis William Cowles and published by . This book was released on 2014 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neurons are born from stem cells, migrate to their final location, form synaptic connections, and terminally differentiate by a process known as neurogenesis. Although this phenomenon is observed in adult organisms across metazoans, most animals lack the ability to repair catastrophic damages to the central nervous system (CNS) caused by injury, disease or aging. By contrast, planarians have the amazing ability to regenerate all tissue types (including the CNS) from a population of pluripotent adult stem cells they maintain throughout their life, making these animals a powerful system to research stem cell-based regeneration in vivo. To investigate how adult stem cells are directed to generate new neurons during CNS regeneration, we examined the basic helix-loop-helix (bHLH) transcription factor family in planarians. Many bHLH family members regulate neurogenesis during development and are associated with nervous system diseases, yet their functions in adult stem cells and mature neurons remain unclear. We identified 44 planarian bHLH homologs, determined their tissue-specific expression in the adult animal, and examined their function using RNA interference. These analyses identified nine bHLHs expressed in stem cells and neurons that were required for CNS regeneration, including homologs of Collier/Olfactory-1/Early B-cell factor (coe), Single-minded (sim), and Hairy enhancer of split (hesl-3). Furthermore, we demonstrated that coe, sim and hesl-3 mRNA were detected in lineage-committed progenitors. Our functional screen revealed that gene silencing of coe results in CNS regeneration defects. COE genes play conserved roles in nervous system development and are associated with CNS diseases; however, the genetic programs downstream of these genes remain largely unknown. By comparing the transcriptome profiles of control and coe-deficient animals, we identified over 900 differentially expressed genes, including 397 downregulated genes enriched for CNS functions. We examined downregulated genes and identified new targets of COE in mature neurons, some of which were required for CNS regeneration. Furthermore, we found novel genes expressed in stem cell progeny that function downstream of COE and were critical for stem cell homeostasis. These findings demonstrate that COE regulates genetic programs essential for CNS homeostasis and regeneration, providing insights into how COE proteins function in the adult nervous system.
Download or read book Cajal s Degeneration and Regeneration of the Nervous System written by Santiago Ramón y Cajal and published by History of Neuroscience. This book was released on 1991 with total page 977 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a reprint of an English translation of Cajal's original work, with abundant notes and commentaries by the editor. This text describes Cajal's fundamental contributions to neuroscience, which continue to be important today. It accurately details Cajal's ideas and data, and providesreaders with the opportunity to learn what Cajal thought about his research career and the significance of his observations. Excerpts from Tello's memorial lectures also provide a contemporary view of Cajal's work.
Download or read book The Chemical Biology of Long Noncoding RNAs written by Stefan Jurga and published by Springer Nature. This book was released on 2020-10-01 with total page 545 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book offers a comprehensive and detailed overview of various aspects of long non-coding RNAs. It discusses their emerging significance in molecular medicine, ranging from human cancers to cardiovascular and metabolic diseases. Transcriptomic studies have demonstrated that the majority of genomes found in complex organisms are expressed in highly dynamic and cell-specific patterns, producing huge numbers of intergenic, antisense and intronic long non-protein-coding RNAs (lncRNAs). Thousands of lncRNAs have been identified, and unlike mRNA, they have no protein-coding capacity. A large repertoire of ncRNAs, actively transcribed from the mammalian genome, control diverse cellular processes, both in terms of development and diseases, through a variety of gene regulatory mechanisms. IncRNAs have emerged as a new paradigm in epigenetic regulation of the genome. Given its scope, the book will be of particular interest to molecular, chemical, cell and developmental biologists, as well as specialists in translational medicine involved in disease-oriented research. It also offers a valuable resource for in silico experts seeking a deeper understanding of lncRNA expression and function through computational analysis of the NGS data.
Download or read book Apoptosis and Beyond written by James A. Radosevich and published by John Wiley & Sons. This book was released on 2018-09-18 with total page 768 pages. Available in PDF, EPUB and Kindle. Book excerpt: These volumes teach readers to think beyond apoptosis and describes all of the known processes that cells can undergo which result in cell death This two-volume source on how cells dies is the first, comprehensive collection to cover all of the known processes that cells undergo when they die. It is also the only one of its kind to compare these processes. It seeks to enlighten those in the field about these many processes and to stimulate their thinking at looking at these pathways when their research system does not show signs of activation of the classic apoptotic pathway. In addition, it links activities like the molecular biology of one process (eg. Necrosis) to another process (eg. apoptosis) and contrasts those that are close to each. Volume 1 of Apoptosis and Beyond: The Many Ways Cells Die begins with a general view of the cytoplasmic and nuclear features of apoptosis. It then goes on to offer chapters on targeting the cell death mechanism; microbial programmed cell death; autophagy; cell injury, adaptation, and necrosis; necroptosis; ferroptosis; anoikis; pyronecrosis; and more. Volume 2 covers such subjects as phenoptosis; pyroptosis; hematopoiesis and eryptosis; cyclophilin d-dependent necrosis; and the role of phospholipase in cell death. Covers all known processes that dying cells undergo Provides extensive coverage of a topic not fully covered before Offers chapters written by top researchers in the field Provides activities that link and contrast processes to each other Apoptosis and Beyond: The Many Ways Cells Die will appeal to students and researchers/clinicians in cell biology, molecular biology, oncology, and tumor biology.
