Download or read book Molecular Mechanism that Leads to Development of Epilepsy by a Sodium Channel Mutation written by Eric Velazquez and published by . This book was released on 2014 with total page 157 pages. Available in PDF, EPUB and Kindle. Book excerpt: The number of mutations in the voltage-gated sodium channel Nav1.1, encoded by SCN1A, that have been associated with genetic epilepsy is extremely high compared to the other sodium channel genes. The crucial function of the voltage-gated sodium channels in the central nervous system (CNS) is to regulate the influx of sodium or sodium current into the neurons. Sodium currents are required for the generation and propagation of action potentials. Subsequently the action potentials cause the release of neurotransmitters that allow the communication and synchronization among neurons in a circuit. Most of the previous mouse models of Scn1a sodium channel mutations result in loss-of-function of sodium currents and decrease of excitability of interneurons. In this study, I investigate the mechanism by which a novel SCN1A mutation, D1886Y, causes epilepsy in a mouse model. Chapter 1 examines the activation, inactivation and dynamics of sodium currents in parvalbumin-expressing (PV+) interneurons from the hippocampus. The Snc1a-D1866Y mutation in these neurons resulted in gain-of-function of sodium current. Chapter 2 investigates how the Snc1a-D1866Y mutation affects the excitability of excitatory and inhibitory neurons to generate action potentials. In PV+ interneurons, the mutation reduced the excitability to fire action potentials. A reduction in action potential firing was also detected in pyramidal neurons, but to a lesser degree. Chapter 3 examines the seizure susceptibility in vivo and in the hippocampal circuit of mice expressing the Snc1a-D1866Y mutation. Our findings suggest the existence of different molecular mechanisms for how Scn1a mutations cause epilepsy. Identification of the molecular mechanisms that lead to epilepsy is crucial for the development of new anti-epileptic drugs.
Download or read book Jasper s Basic Mechanisms of the Epilepsies written by Jeffrey Noebels and published by OUP USA. This book was released on 2012-06-29 with total page 1258 pages. Available in PDF, EPUB and Kindle. Book excerpt: Jasper's Basic Mechanisms, Fourth Edition, is the newest most ambitious and now clinically relevant publishing project to build on the four-decade legacy of the Jasper's series. In keeping with the original goal of searching for "a better understanding of the epilepsies and rational methods of prevention and treatment.", the book represents an encyclopedic compendium neurobiological mechanisms of seizures, epileptogenesis, epilepsy genetics and comordid conditions. Of practical importance to the clinician, and new to this edition are disease mechanisms of genetic epilepsies and therapeutic approaches, ranging from novel antiepileptic drug targets to cell and gene therapies.
Download or read book Channelopathies of the Nervous System written by Michael Rose and published by Butterworth-Heinemann. This book was released on 2001 with total page 376 pages. Available in PDF, EPUB and Kindle. Book excerpt: * A unique reference focusing on the rapidly developing field of channelopathies of common neurological disorders * Written specifically for the clinical neurologist and neuroscientist * It reviews the underlying scientific principles of ion channel function and the current research and its clinical applications
Download or read book An Epilepsy causing Human Sodium Channel Mutation Reduces Activity in Inhibitory Neurons written by Karoni Dutt and published by . This book was released on 2010 with total page 125 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epileptic seizures are the result of abnormal synchronized electrical discharges within the Central Nervous System (CNS). One type of epilepsy is Genetic Epilepsy with Febrile Seizures Plus (GEFS+) which is inherited as an autosomal dominant disorder. The R1648H mutation of the SCN1A sodium channel gene, among several others, causes GEFS+. The SCN1A gene encodes the pore forming & alpha subunit of the voltage gated Nav1.1 sodium channel in the CNS, which underlies the generation of the action potential upstroke. Our lab and others have reported gain-of-function defects owing to abnormal inactivation of the R1648H mutant using heterologous expression systems. However, this approach does not give an idea of the effects of the mutant in the native neuronal environment or of the cellular dynamic processes actually involved in epileptogenesis. Our goal was to determine the effect of the Nav1.1 channel mutation at the molecular, cellular and network levels using a mouse model, to provide insights into the mechanisms of seizures in GEFS+. To accomplish this, we constructed a transgenic mouse expressing R1648H Nav1.1 channels under the native promoter. The transgenic channels are also resistant to saxitoxin, so that the mutant channel properties can be studied in isolation from the toxin sensitive endogenous sodium channels. We studied the changes in sodium channel gating properties of mutant channels in the presence of saxitoxin in dissociated neurons from transgenic mice. We found reduced sodium channel activity in cortical bipolar-shaped neurons from R1648H transgenic mice compared to the wild-type mice. However, in the transgenic mice, the Nav1.1 channels are over-expressed and thus it is not a good model for the human disease. Therefore, we constructed a knock-in mouse model carrying the same R1648H mutation in Nav1.1 channels. We studied the effect of the mutation on sodium channel properties in cortical neurons and found loss-of-function defects in bipolar-shaped interneurons, which led us to predict reduced firing frequency in these neurons. Current clamp experiments showed that mutant interneurons have significant difficulty in sustaining repetitive firing. This decreased firing and might lead to reduced inhibition and failure to suppress hyperactivity in excitatory neurons, thus resulting to seizures in GEFS+.
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 The Causes of Epilepsy written by Simon Shorvon and published by Cambridge University Press. This book was released on 2019-05-02 with total page 1013 pages. Available in PDF, EPUB and Kindle. Book excerpt: Expanded and revised, this unique book provides concise descriptions of the many causes of epilepsy, for use in clinical practice.
Download or read book Genetics of Epilepsy written by and published by Elsevier. This book was released on 2014-09-04 with total page 346 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book chapters cover different aspects of epilepsy genetics, starting with the "classical" concept of epilepsies as ion channel disorders. The second part of the book gives credit to the fact that by now non-ion channel genes are recognized as equally important causes of epilepsy. The concluding chapters are designed to offer the reader insight into current methods in epilepsy research. Each chapter is self-contained and deals with a selected topic of interest. Authors are the leading experts in the field of epilepsy research Book covers the most important aspects of epilepsy Interesting for both scientists and clinicians
Download or read book Voltage Gated Sodium Channels written by Peter C. Ruben and published by Springer Science & Business Media. This book was released on 2014-04-15 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: A number of techniques to study ion channels have been developed since the electrical basis of excitability was first discovered. Ion channel biophysicists have at their disposal a rich and ever-growing array of instruments and reagents to explore the biophysical and structural basis of sodium channel behavior. Armed with these tools, researchers have made increasingly dramatic discoveries about sodium channels, culminating most recently in crystal structures of voltage-gated sodium channels from bacteria. These structures, along with those from other channels, give unprecedented insight into the structural basis of sodium channel function. This volume of the Handbook of Experimental Pharmacology will explore sodium channels from the perspectives of their biophysical behavior, their structure, the drugs and toxins with which they are known to interact, acquired and inherited diseases that affect sodium channels and the techniques with which their biophysical and structural properties are studied.
Download or read book Epileptic Syndromes in Infancy Childhood and Adolescence 5th edition written by Bureau Michelle and published by John Libbey Eurotext. This book was released on 2012-11-12 with total page 682 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ultimate reference book : the 5th updated edition of the famous “blue guide”. Incluided : A DVD with new sequences completes each chapter! Epileptology changes. The syndromic approach is completed by an etiological approach, based on the major advances in genetics and functional genetics. New entities have found their place, and a purely descriptive, “electroclinical” approach is no longer adapted in many circumstances. The 5th edition of the Blue Guide includes the most recent advances. It was necessary to justify the physiological, epidemiologic, genetic and therapeutic approaches and to consider them in the light of the new classification efforts, which are still in the making. Nevertheless, the description of epileptic syndromes, both classical and recent, remains at the core of this book.
Download or read book Ion Channel Diseases written by and published by Academic Press. This book was released on 2011-09-06 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ion channel dysfunction in humans leads to impairment of the excitable processes necessary for the normal function of several tissues, such as muscle and brain. It follows that an increasing number of human diseases have been associated with malfunctioning ion channels, many of which have a genetic component. This volume of Advances in Genetics presents a broad and comprehensive overview of the inherited channelopathies in humans, including clinical, genetic and molecular aspects of these conditions. Keeping true to the scope of the serial, novel genomic and modeling research approaches and a review of potential therapeutic approaches for each of these conditions are also incorporated.
Download or read book Astrocytes and Epilepsy written by Jacqueline A. Hubbard and published by Academic Press. This book was released on 2016-07-05 with total page 395 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epilepsy is a devastating group of neurological disorders characterized by periodic and unpredictable seizure activity in the brain. There is a critical need for new drugs and approaches given than at least one-third of all epilepsy patients are not made free of seizures by existing medications and become "medically refractory". Much of epilepsy research has focused on neuronal therapeutic targets, but current antiepileptic drugs often cause severe cognitive, developmental, and behavioral side effects. Recent findings indicate a critical contribution of astrocytes, star-shaped glial cells in the brain, to neuronal and network excitability and seizure activity. Furthermore, many important cellular and molecular changes occur in astrocytes in epileptic tissue in both humans and animal models of epilepsy. The goal of Astrocytes and Epilepsy is to comprehensively review exciting findings linking changes in astrocytes to functional changes responsible for epilepsy for the first time in book format. These insights into astrocyte contribution to seizure susceptibility indicate that astrocytes may represent an important new therapeutic target in the control of epilepsy. Astrocytes and Epilepsy includes background explanatory text on astrocyte morphology and physiology, epilepsy models and syndromes, and evidence from both human tissue studies and animal models linking functional changes in astrocytes to epilepsy. Beautifully labelled diagrams are presented and relevant figures from the literature are reproduced to elucidate key findings and concepts in this rapidly emerging field. Astrocytes and Epilepsy is written for neuroscientists, epilepsy researchers, astrocyte investigators as well as neurologists and other specialists caring for patients with epilepsy. Presents the first comprehensive book to synthesize historical and recent research on astrocytes and epilepsy into one coherent volume Provides a great resource on the field of astrocyte biology and astrocyte-neuron interactions Details potential therapeutic targets, including chapters on gap junctions, water and potassium channels, glutamate and adenosine metabolism, and inflammation
Download or read book Epilepsy Across the Spectrum written by Institute of Medicine and published by National Academies Press. This book was released on 2012-07-29 with total page 568 pages. Available in PDF, EPUB and Kindle. Book excerpt: Although epilepsy is one of the nation's most common neurological disorders, public understanding of it is limited. Many people do not know the causes of epilepsy or what they should do if they see someone having a seizure. Epilepsy is a complex spectrum of disorders that affects an estimated 2.2 million Americans in a variety of ways, and is characterized by unpredictable seizures that differ in type, cause, and severity. Yet living with epilepsy is about much more than just seizures; the disorder is often defined in practical terms, such as challenges in school, uncertainties about social situations and employment, limitations on driving, and questions about independent living. The Institute of Medicine was asked to examine the public health dimensions of the epilepsies, focusing on public health surveillance and data collection; population and public health research; health policy, health care, and human services; and education for people with the disorder and their families, health care providers, and the public. In Epilepsy Across the Spectrum, the IOM makes recommendations ranging from the expansion of collaborative epilepsy surveillance efforts, to the coordination of public awareness efforts, to the engagement of people with epilepsy and their families in education, dissemination, and advocacy for improved care and services. Taking action across multiple dimensions will improve the lives of people with epilepsy and their families. The realistic, feasible, and action-oriented recommendations in this report can help enable short- and long-term improvements for people with epilepsy. For all epilepsy organizations and advocates, local, state, and federal agencies, researchers, health care professionals, people with epilepsy, as well as the public, Epilepsy Across the Spectrum is an essential resource.
Download or read book Translational Research in Traumatic Brain Injury written by Daniel Laskowitz and published by CRC Press. This book was released on 2016-04-21 with total page 388 pages. Available in PDF, EPUB and Kindle. Book excerpt: Traumatic brain injury (TBI) remains a significant source of death and permanent disability, contributing to nearly one-third of all injury related deaths in the United States and exacting a profound personal and economic toll. Despite the increased resources that have recently been brought to bear to improve our understanding of TBI, the developme
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 The Na K ATPase written by Jean-Daniel Horisberger and published by R. G. Landes. This book was released on 1994 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text addresses the question, How does the sodium pump pump'. A variety of primary structure information is available, and progress has been made in the functional characterization of the Na, K-pump, making the answer to this question possible, within reach of currently used techniques
Download or read book Human Pathobiochemistry written by Toshitaka Oohashi and published by Springer. This book was released on 2019-03-13 with total page 349 pages. Available in PDF, EPUB and Kindle. Book excerpt: This textbook uses a case-study approach to present the core principles of biochemistry and molecular biology in the context of human disease to students who will be involved in patient care. The 29 clinical cases have been carefully selected to cover key scientific concepts and some common, and other not so common, diseases. While the principal focus is on topics relating to metabolic disease, further subjects such as connective tissue disorders, neurological disorders, auto-inflammatory disorders, infective diseases, and cancer are also addressed. Each chapter provides a specific patient report that includes the natural history, pertinent clinical laboratory data, physical findings, subsequent diagnosis, and therapy. This is followed by a comprehensive discussion of the normal biochemical processes and reactions pertaining to the case, along with the pathophysiological mechanisms of the disease. Graphical diagrams are provided in each chapter for ease of comprehension.
Download or read book Polyglutamine Disorders written by Clévio Nóbrega and published by Springer. This book was released on 2018-02-09 with total page 467 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a cutting-edge review of polyglutamine disorders. It primarily focuses on two main aspects: (1) the mechanisms underlying the pathologies’ development and progression, and (2) the therapeutic strategies that are currently being explored to stop or delay disease progression. Polyglutamine (polyQ) disorders are a group of inherited neurodegenerative diseases with a fatal outcome that are caused by an abnormal expansion of a coding trinucleotide repeat (CAG), which is then translated in an abnormal protein with an elongated glutamine tract (Q). To date, nine polyQ disorders have been identified and described: dentatorubral-pallidoluysian atrophy (DRPLA); Huntington’s disease (HD); spinal–bulbar muscular atrophy (SBMA); and six spinocerebellar ataxias (SCA 1, 2, 3, 6, 7, and 17). The genetic basis of polyQ disorders is well established and described, and despite important advances that have opened up the possibility of generating genetic models of the disease, the mechanisms that cause neuronal degeneration are still largely unknown and there is currently no treatment available for these disorders. Further, it is believed that the different polyQ may share some mechanisms and pathways contributing to neurodegeneration and disease progression.
