Download or read book Mechanisms Underlying the CNS Myelination written by Nicolas Snaidero and published by . This book was released on 2014 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid axonal electrical impulse propagation. Both light and electron microscopy have been used to describe morphological features of the myelin sheath. However, the underlying mechanisms of myelin wrapping are still unclear and remain under debate. To investigate the morphology of the CNS myelin sheath during its formation we made use of multiple imaging techniques such as focus ion beam milling coupled to scanning electron microscopy, live imaging, transmission electron microscopy, cryo-immuno ...
Download or read book Seizures and Epilepsy written by Jerome Engel Jr and published by Oxford University Press. This book was released on 2013-01-31 with total page 737 pages. Available in PDF, EPUB and Kindle. Book excerpt: This second edition of 'Seizures and Epilepsy' is completely revised, due to tremendous advances in the understanding of the fundamental neuronal mechanisms underlying epileptic phenomena, as well as current diagnosis and treatment, which have been heavily influenced over the past several decades by seminal neuroscientific developments, particularly the introduction of molecular neurobiology, genetics, and modern neuroimaging. This resource covers a broad range of both basic and clinical epileptology.
Download or read book Netter s Atlas of Neuroscience written by David L. Felten and published by Elsevier Health Sciences. This book was released on 2015-11-30 with total page 499 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ideal for students of neuroscience and neuroanatomy, the new edition of Netter's Atlas of Neuroscience combines the didactic well-loved illustrations of Dr. Frank Netter with succinct text and clinical points, providing a highly visual, clinically oriented guide to the most important topics in this subject. The logically organized content presents neuroscience from three perspectives: an overview of the nervous system, regional neuroscience, and systemic neuroscience, enabling you to review complex neural structures and systems from different contexts. You may also be interested in: A companion set of flash cards, Netter's Neuroscience Flash Cards, 3rd Edition, to which the textbook is cross-referenced. Coverage of both regional and systemic neurosciences allows you to learn structure and function in different and important contexts. Combines the precision and beauty of Netter and Netter-style illustrations to highlight key neuroanatomical concepts and clinical correlations. Reflects the current understanding of the neural components and supportive tissue, regions, and systems of the brain, spinal cord, and periphery. Uniquely informative drawings provide a quick and memorable overview of anatomy, function, and clinical relevance. Succinct and useful format utilizes tables and short text to offer easily accessible "at-a-glance" information. Provides an overview of the basic features of the spinal cord, brain, and peripheral nervous system, the vasculature, meninges and cerebrospinal fluid, and basic development. Integrates the peripheral and central aspects of the nervous system. Bridges neuroanatomy and neurology through the use of correlative radiographs. Highlights cross-sectional brain stem anatomy and side-by-side comparisons of horizontal sections, CTs and MRIs. Features video of radiograph sequences and 3D reconstructions to enhance your understanding of the nervous system. Student Consult eBook version included with purchase. This enhanced eBook experience includes access -- on a variety of devices -- to the complete text, 14 videos, and images from the book. Expanded coverage of cellular and molecular neuroscience provides essential guidance on signaling, transcription factors, stem cells, evoked potentials, neuronal and glial function, and a number of molecular breakthroughs for a better understanding of normal and pathologic conditions of the nervous system. Micrographs, radiologic imaging, and stained cross sections supplement illustrations for a comprehensive visual understanding. Increased clinical points -- from sleep disorders and inflammation in the CNS to the biology of seizures and the mechanisms of Alzheimer's -- offer concise insights that bridge basic neuroscience and clinical application.
Download or read book From Neurons to Neighborhoods written by National Research Council and published by National Academies Press. This book was released on 2000-11-13 with total page 610 pages. Available in PDF, EPUB and Kindle. Book excerpt: How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media. How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a working family, the effect of politics on programs for children, the costs and benefits of intervention, and other issues. The committee issues a series of challenges to decision makers regarding the quality of child care, issues of racial and ethnic diversity, the integration of children's cognitive and emotional development, and more. Authoritative yet accessible, From Neurons to Neighborhoods presents the evidence about "brain wiring" and how kids learn to speak, think, and regulate their behavior. It examines the effect of the climate-family, child care, community-within which the child grows.
Download or read book The Biology of Oligodendrocytes written by Patricia Armati and published by Cambridge University Press. This book was released on 2010-10-21 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Traditionally, oligodendrocytes have been assumed to play a minor supporting role in the central nervous system and their importance has generally been overlooked. For the first time, this book provides a dedicated review of all of the major aspects of oligodendrocyte biology, including development, organization, genetics, and immunobiology. Later chapters emphasize the importance of this underestimated cell to the mammalian central nervous system by exploring the role of myelin synthesis and maintenance in neural disease and repair. Particular attention is paid to multiple sclerosis (MS), arguably the prime example of an acquired demyelinating disease, with detailed examinations of the current concepts regarding demyelination, oligodendroglial damage, and remyelination in MS lesions.
Download or read book Mechanisms of Myelination It s All about the Matrix written by Sarah Degenova Ackerman and published by . This book was released on 2016 with total page 293 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin, the lipid-rich sheath that insulates axons to facilitate rapid conduction of action potentials, is generated by specialized glial cells -- oligodendrocytes (OLs) in the central nervous system (CNS) and Schwann cells (SCs) in the peripheral nervous system (PNS). The importance of myelin is underscored by the devastating symptoms experienced by patients who suffer from demyelinating diseases of the PNS (e.g., Charcot-Marie-Tooth disease) and CNS (e.g., multiple sclerosis, MS). The molecular mechanisms governing myelination are not fully understood, yet several studies implicate extracellular matrix (ECM) proteins and their receptors as important regulators of these processes (reviewed in Chapter 1 of this thesis). In my thesis work, I used both forward and reverse genetics to define two new regulators of myelination with links to the ECM: GPR56 and ADAMTS9. GPR56 belongs to a specialized class of G protein-coupled receptors (GPCRs) called the adhesion GPCRs (aGCPRs). aGPCRs mediate both cell-cell and cell-matrix interactions, and thus could play a role in myelinating glial cells. I used zebrafish and mouse models to define the function of GPR56 in both OL and SC development and myelination. First, I explore the function of Gpr56 in the CNS in zebrafish and show that gpr56 is robustly expressed in early stages of OL development. In addition, I demonstrate that impaired Gpr56 function results in a significant reduction of OL number and of myelination due to decreased proliferation of OL precursor cells, and that these functions of Gpr56 are mediated via interactions with G[alpha]12/13 proteins and RhoA activation (Ackerman et al. 2015, Nat Commun; Chapter 2 of this thesis). In contrast, diminished GPR56 function in the PNS of zebrafish and mouse mutants does not result in hypomyelination. Instead, loss of Gpr56 causes defects in axon-SC interactions during development, myelin structural abnormalities, and impaired myelin maintenance. Importantly, these developmental defects result in axon degeneration and progressive neuropathy in adult Gpr56 mutants (Ackerman et al., in revision; Chapter 3 of this thesis). As mutations in GPR56 in humans cause neurological disorders that can present with PNS pathology, my work defines Gpr56 as a novel, clinically relevant regulator of nervous system health. In a separate yet complimentary line of work, I conducted a large scale forward genetic screen in zebrafish in collaboration with members of the Monk and Solnica-Krezel laboratories and identified the secreted matrix metalloprotease ADAMTS9 as a critical new regulator of OL myelination. ADAMTS9 normally functions to cleave chondroitin sulfate proteoglycans (CSPGs) in the ECM, and accumulation of CSPGs is a major cause of failed axon regrowth and remyelination after CNS injury and in demyelinating plaques of MS brains. Excitingly, I find that myelin is lost in adamts9 zebrafish mutants concurrently with engulfment of OL lineage cells (including mature, myelinating OLs) by phagocytic immune cells, and that these phenotypes can be ameliorated upon removal of CSPGs from the ECM (Ackerman et al., in preparation; Chapter 4 of this thesis). MS is a complex, autoimmune disease in which the immune system attacks the OL myelin sheath, and the cause of this attack is unknown. Thus, the identification of ADAMTS9 as a critical regulator of OL-immune cell interactions represents a major advancement in our understanding of CNS demyelination, and may present a new therapeutic target for MS. In sum, my thesis work defined the roles of two previously unappreciated regulators of myelination, GPR56 and ADAMTS9, and further emphasized the importance of the extracellular matrix in modulating the development of myelinating glial cells.
Download or read book Molecular Mechanisms of Myelin Dysfunctions in the Nervous System written by Jihyun Kim and published by . This book was released on 2017 with total page 166 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin is generated by Schwann cells (SCs) in the peripheral nervous system (PNS) and by oligodendrocytes (OLs) in the central nervous system (CNS). Myelin not only provides physical and structural support to the axon, it also provides trophic and metabolic supports. In addition, myelin is important for rapid nerve conduction, which is essential for proper communication within a neuronal circuit. Therefore, damage to myelin or myelin loss disrupts axonal integrity and impairs neuronal functions. Elucidating molecular mechanisms underlying myelin defects under pathological conditions will be important in gaining insights into developing a strategy for preventing myelin loss and improving myelin repair. In this study, we investigated molecular mechanisms of aberrant myelination and myelin loss associated with Charcot Marie Tooth disease (CMT) in the PNS and traumatic brain injury (TBI) in the CNS. In Chapter 1, we investigated the impact of CMT4B1-associated MTMR2 loss in SCs. CMT4B1 is a genetically inherited disorder of the PNS that is caused by loss of MTMR2 gene function. In CMT4B1 patients, myelin outfolding and demyelination are observed resulting in decreased nerve conduction, muscle weakness, atrophy, and sensory deficits. Previously, it has been shown that SC-specific deletion of MTMR2 in mice results in reduced nerve conduction and myelin abnormalities similar to defects observed in CMT4B1patients. However, the mechanism(s) by which loss of MTMR2 function leads to the myelin abnormalities are not fully understood. To elucidate the underlying mechanisms, we generated MTMR2 knockdown SCs and analyzed the effect of MTMR2 loss on intracellular signaling pathways that are essential for SC myelination. Since MTMR2 is a phosphoinositide 3-phosphatase that regulates the PI(3,5)P2 metabolism, it is possible that abnormal regulation of the PI(3,5)P2 level in MTMR2 KD SCs may be associated with the aberrant SC functions. Recently, PI(3,5)P2 has been shown to serve as a platform for mTORC1 signaling on lysosomal membrane. Since mTORC1 has an important role in SC myelination, we monitored whether MTMR2 loss affects the mTORC1 signaling pathway in SCs. Here, we report an aberrant increase in mTORC1 activity in MTMR2 KD SCs. The mTORC1 activation is also associated with inhibition of autophagy and transcription activity of TFEB, a regulator of lysosomal biogenesis and function. Myelin repair or promoting remyelination in the PNS is important for improving neuronal function in patients with peripheral myelin dysfunctions. In Chapter 2, we elucidated the promyelination function of recombinant TIMP-3 in SCs. TIMP-3 is a member of the tissue inhibitor of metalloproteinase family proteins and one of the targets includes ADAM17. Endogenous ADAM17 in the PNS negatively regulate axonal Nrg1 type III signaling that is essential for SC myelination. Here, we report that recombinant TIMP-3 enhances myelin formation by SCs. The TIMP-3 function is associated with an increase in axonal Nrg1 signaling and laminin deposition during the early stages of myelin formation. In Chapter 3, we investigated molecular mechanisms underlying myelin dysfunction in the CNS associated with TBI. Myelin loss following TBI contributes to axonal degeneration, neuronal death and in long-term, neuronal dysfunction in the patients. Recent studies provide evidence that primary myelin loss contributes to the myelinated axon pathology following TBI. The myelin loss appears to occur without OL death, indicating that demyelination results from a mechanism that actively destroys myelin in viable OLs. Therefore, understanding the mechanisms of OL response to injury may provide insights into preventing demyelination and/or to protecting proper axon- myelin units following TBI. To this end, we investigated the direct impact of mechanical injury on OLs. We developed an OL monoculture system established on a deformable silicone membrane that can be rapidly stretched by a computer-controlled air pulse, which mimics diffused mechanical injury in the brain following TBI. Our data show that stretch injury induces activation of the Erk1/2 pathway in OLs, which leads to myelin protein loss. Furthermore, the Erk1/2 activation was induced by intracellular calcium increase. Inhibition of Erk1/2 or chelating intracellular calcium prevents myelin protein loss after stretch injury. Furthermore, TBI in vivo results in rapid Erk1/2 activation in white matter OLs accompanied by losing the mature OL phenotype. By studying the molecular mechanisms responsible for myelin malformation or myelin loss in demyelinating diseases, we provide evidences of signaling pathways or signaling molecules that could be potential therapeutic targets for preventing myelin dysfunctions.
Download or read book Introduction to Epilepsy written by Gonzalo Alarcón and published by Cambridge University Press. This book was released on 2012-04-26 with total page 641 pages. Available in PDF, EPUB and Kindle. Book excerpt: Covers all aspects of epilepsy, from basic mechanisms to diagnosis and management, as well as legal and social considerations.
Download or read book Oligodendrocyte Development and CNS Myelination in Development and Injuries written by Qiang Zhu and published by . This book was released on 2011 with total page 356 pages. Available in PDF, EPUB and Kindle. Book excerpt: Myelin is critical for the rapid conduction of action potentials in the vertebrate nervous system. The oligodendrocyte is the cell type responsible for producing myelin and ensheathing axons in central nervous system (CNS). The myelination process is highly regulated by a number of extrinsic and intrinsic mechanisms during normal development of the oligodendrocyte lineage. Deficiencies in the mechanisms underlying oligodendrocyte specification, differentiation or maturation can cause myelination disorders. Moreover, it is clear that many of the mechanisms that regulate developmental myelination also have conservative roles in injury-induced remyelination process. Therefore, deciphering the mechanisms controlling oligodendrocyte development is not only important for understanding how myelination is regulated during CNS development, but also has enormous implications in developing therapies to promote remyelination in demyelinating diseases such as multiple sclerosis and spinal cord injury. The major purpose of this dissertation is to study how the differentiation and myelin gene expression of oligodendrocytes are regulated at transcriptional level as well as contributions of oligodendrocytes from different origins to CNS myelination, and the role of surface molecules in developmental myelination or remyelination. In the first part, I used the cre-loxP transgenic labeling system to trace the cell fate of dorsally-derived oligodendrocytes during development and under pathologic conditions, and revealed their critical contributions to axonal myelination and remyelination. In the second part, the tetracycline-inducible system was utilized to control the over-expression of Nkx2.2 transcription factor in oligodendrocyte lineage cells at different developmental stages, and revealed a stage-dependent function for Nkx2.2 in oligodendrocyte differentiation and myelin gene expression. In the final part, I demonstrated that protein tyrosine phosphate receptor type D (PTPRD) is selectively expressed in differentiated oligodendrocytes, and loss-of-function analysis suggested that PTPRD plays an important role in early CNS myelination and possibly in myelin regenerative process as well.
Download or read book Signaling Mechanisms Underlying Inhibition of Axonal Regeneration by CNS Myelin written by Kevin Chun-Kai Wang and published by . This book was released on 2003 with total page 174 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Glial Cells in Health and Disease of the CNS written by Rommy von Bernhardi and published by Springer. This book was released on 2016-10-06 with total page 349 pages. Available in PDF, EPUB and Kindle. Book excerpt: A timely overview covering the three major types of glial cells in the central nervous system - astrocytes, microglia, and oligodendrocytes. New findings on glia biology are overturning a century of conventional thinking about how the brain operates and are expanding our knowledge about information processing in the brain. The book will present recent research findings on the role of glial cells in both healthy function and disease. It will comprehensively cover a broad spectrum of topics while remaining compact in size.
Download or read book Neuroprotection in Alzheimer s Disease written by Illana Gozes and published by Academic Press. This book was released on 2016-12-30 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: Neuroprotection in Alzheimer’s Disease offers a translational point-of-view from both basic and clinical standpoints, putting it on the cusp for further clinical development with its emphasis on nerve cell protection, including the accumulation of knowledge from failed clinical trials and new advances in disease management. This book brings together the latest findings, both basic, and clinical, under the same cover, making it easy for the reader to obtain a complete overview of the state-of-the-field and beyond. Alzheimer's disease is the most common form of dementia, accounting for 60 to 80 percent of dementia cases. It is a progressive brain disease that slowly destroys memory, thinking skills, and eventually, even the ability to carry out the simplest tasks. It is characterized by death of synapses coupled to death nerve cells and brain degeneration which is manifested by loss of cognitive abilities. Understanding neuroprotection in Alzheimer’s disease will pave the path to better disease management and novel therapeutics. Comprehensive reference detailing neuroprotection in Alzheimer’s Disease, with details on nerve cell protection and new advances in disease management Combines the knowledge and points-of-view of both medical doctors and basic scientists, putting the subject at the forefront for further clinical development Edited by one of the leading researchers in Alzheimer’s Disease
Download or read book Environmental Neurotoxicology written by National Research Council and published by National Academies Press. This book was released on 1992-02-01 with total page 167 pages. Available in PDF, EPUB and Kindle. Book excerpt: Scientists agree that exposure to toxic agents in the environment can cause neurological and psychiatric illnesses ranging from headaches and depression to syndromes resembling parkinsonism. It can even result in death at high exposure levels. The emergence of subclinical neurotoxicity-the concept that long-term impairments can escape clinical detection-makes the need for risk assessment even more critical. This volume paves the way toward definitive solutions, presenting the current consensus on risk assessment and environmental toxicants and offering specific recommendations. The book covers: The biologic basis of neurotoxicity. Progress in the application of biologic markers. Reviews of a wide range of in vitro and in vivo testing techniques. The use of surveillance and epidemiology to identify neurotoxic hazards that escape premarket screening. Research needs. This volume will be an important resource for policymakers, health specialists, researchers, and students.
Download or read book Multiple Sclerosis written by Institute of Medicine and published by National Academies Press. This book was released on 2001-08-10 with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is a chronic and often disabling disease of the nervous system, affecting about 1 million people worldwide. Even though it has been known for over a hundred years, no cause or cure has yet been discovered-but now there is hope. New therapies have been shown to slow the disease progress in some patients, and the pace of discoveries about the cellular machinery of the brain and spinal cord has accelerated. This book presents a comprehensive overview of multiple sclerosis today, as researchers seek to understand its processes, develop therapies that will slow or halt the disease and perhaps repair damage, offer relief for specific symptoms, and improve the abilities of MS patients to function in their daily lives. The panel reviews existing knowledge and identifies key research questions, focusing on: Research strategies that have the greatest potential to understand the biological mechanisms of recovery and to translate findings into specific strategies for therapy. How people adapt to MS and the research needed to improve the lives of people with MS. Management of disease symptoms (cognitive impairment, depression, spasticity, vision problems, and others). The committee also discusses ways to build and financially support the MS research enterprise, including a look at challenges inherent in designing clinical trials. This book will be important to MS researchers, research funders, health care advocates for MS research and treatment, and interested patients and their families.
Download or read book The Biology of Multiple Sclerosis written by Gregory Atkins and published by Cambridge University Press. This book was released on 2012-11-08 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is the most common debilitating neurological disease in people under the age of forty in the developed world. Many publications cover medical and clinical approaches to the disease; however, The Biology of Multiple Sclerosis provides a clear and concise up-to-date overview of the scientific literature on the various theories of MS pathogenesis. Covering the main elements of scientific research into multiple sclerosis, the book contains chapters on the neuropathology of the disease as well as an account of the most extensively used animal model experimental autoimmune encephalomyelitis. The book contains chapters regarding the role of viruses in the development of multiple sclerosis. Viruses have long been implicated and chapters on animal models based on virus infection, as well as their possible role in the etiology of MS, are included. Of interest to MS researchers, the book is written to also be of value to postgraduate and medical students.
Download or read book Mechanisms of the Glaucomas written by Joyce Tombran-Tink and published by Springer Science & Business Media. This book was released on 2008-06-06 with total page 747 pages. Available in PDF, EPUB and Kindle. Book excerpt: The purpose of this important new book is to provide basic scientists working in the field of glaucoma with a current understanding of the clinical aspects of glaucoma. The authors comprehensively review the most current knowledge available in the field and provide a basis in which researchers can effectively study the glaucomas. The multidisciplinary book will be of great value as its contents will aid the reader in prevention of blindness from glaucoma.
Download or read book A History of Nerve Functions written by Sidney Ochs and published by Cambridge University Press. This book was released on 2004-04-19 with total page 452 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent developments have extended our knowledge of the basic functions of nerves: notably, the demonstration of the mechanism within nerve fibers which transports a wide range of essential materials. In order to understand how this discovery occurred, it is necessary to examine its history. The story begins in ancient Greece when nerves were conceived of as channels through which animal spirits carried sensory impressions to the brain. As science developed, the discoveries of various physical and chemical agents supplanted the agency of animal spirits until the molecular machinery of transport was recognized. In this fascinating and complete history, Sidney Ochs begins with a chronological look at this path of discovery, followed in the second half by a thematic approach wherein the author describes the electrical nature of the nerve impulse, fiber form and its changes in degeneration and regeneration, reflexes, learning, memory and other higher functions in which transport participates.
