Glial Amino Acid Transporters
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Glial Amino Acid Transporters
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Author : Arturo Ortega
language : en
Publisher: Springer
Release Date : 2017-08-21
Glial Amino Acid Transporters written by Arturo Ortega and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-08-21 with Medical categories.
This ambitious compendium provides an extensive overview on the "supporting cells" of the vertebrate central nervous system, these being glial cells which far outnumber neurons but are much less understood. Covering multiple aspects of this family of transporters-- from structural properties, to their involvement in signaling and gene expression regulation, this volume presents the most recent research on the roles of glial amino acid transporters as key molecules of brain metabolism and signaling.
The Glutamate Gaba Glutamine Cycle
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Author : Arne Schousboe
language : en
Publisher: Springer
Release Date : 2016-11-25
The Glutamate Gaba Glutamine Cycle written by Arne Schousboe and has been published by Springer this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-11-25 with Medical categories.
Fundamental biochemical studies of basic brain metabolism focusing on the neuroactive amino acids glutamate and GABA combined with the seminal observation that one of the key enzymes, glutamine synthetase is localized in astroglial cells but not in neurons resulted in the formulation of the term “The Glutamate-Glutamine Cycle.” In this cycle glutamate released from neurons is taken up by surrounding astrocytes, amidated by the action of glutamine synthetase to glutamine which can be transferred back to the neurons. The conversion of glutamate to glutamine is like a stealth technology, hiding the glutamate molecule which would be highly toxic to neurons due to its excitotoxic action. This series of reactions require the concerted and precise interaction of a number of enzymes and plasma membrane transporters, and this volume provides in-depth descriptions of these processes. Obviously such a series of complicated reactions may well be prone to malfunction and therefore neurological diseases are likely to be associated with such malfunction of the enzymes and transporters involved in the cycle. These aspects are also discussed in several chapters of the book. A number of leading experts in neuroscience including intermediary metabolism, enzymology and transporter physiology have contributed to this book which provides comprehensive discussions of these different aspects of the functional importance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to basic aspects of brain energy metabolism. This book will be of particular importance for students as well as professionals interested in these fundamental processes involved in brain function and dysfunction.
Astrocytes And Epilepsy
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Author : Jacqueline A. Hubbard
language : en
Publisher: Academic Press
Release Date : 2016-07-05
Astrocytes And Epilepsy written by Jacqueline A. Hubbard and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2016-07-05 with Medical categories.
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
Investigating The Physiological Role Of Chloride Permeation Through Excitatory Amino Acid Transporter 1 Eaat1
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Author : Muhammad Azman Akhter
language : en
Publisher:
Release Date : 2019
Investigating The Physiological Role Of Chloride Permeation Through Excitatory Amino Acid Transporter 1 Eaat1 written by Muhammad Azman Akhter and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019 with categories.
"Astrocytes maintain ion and neurotransmitter homeostasis within the central nervous system. They do so by expressing channels, receptors and transporters such as excitatory amino acid transporters (EAATs) along their highly ramified arbours. EAATs are well known to be glutamate transporters, but they have a dual function as chloride channels. The conservation of the EAAT anion channel from GltPh in prokaryotes to mammals suggests an essential physiological role. However, few studies have addressed the role of chloride permeation through EAAT1 in vivo, so its importance for normal brain function is not yet completely understood.During my project, I built tools to separate the chloride channel and glutamate transport functions of the human EAAT1 (hEAAT1) protein. Through an extensive literature review, I identified a series of hEAAT1 mutations that only affect the permeation and gating properties of the Cl- channel, without affecting glutamate transport function. I built transgenic flies where these altered hEAAT1 proteins were expressed in Drosophila astrocytes in vivo. Additionally, I built transgenic flies to investigate the contribution of hEAAT1 Cl- channel in the cytopathology of Episodic Ataxia Type 6 using five new patient-derived mutations. Using an antibody to hEAAT1, I first validated the expression and proper localization of these altered hEAAT1 proteins within glial cells. Additionally, I developed an improved and optimized method to quantify the crawling behaviour of L1 larvae. With this locomotion assay, I showed that EAAT1 is required in astrocytes for motor behavior, and that ensheathing glia provide an EAAT1-mediated function that is essential for animal survival. Using these transgenic flies coupled with the new locomotion assay, our lab is poised to determine the physiological role of hEAAT1 Cl- channel in glial cells. Our preliminary data provide the first direct evidence that the hEAAT1 Cl- channel is essential for its function in glial cells in vivo under physiological conditions"--
Peptide And Amino Acid Transport Mechanisms In The Central Nervous System
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Author : Ljubiša Rakić
language : en
Publisher: Stockton Press
Release Date : 1988
Peptide And Amino Acid Transport Mechanisms In The Central Nervous System written by Ljubiša Rakić and has been published by Stockton Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 1988 with Science categories.
Addresses the regulation, within the brain extracellular fluid, of peptide and amino acid levels, particularly neurotransmitters and neuromodulators. Particular attention is devoted to the way in which peptides may either penetrate the blood-brain barrier or alter its permeability to other solutes. Focuses on central nervous system disease, especially in designing drugs and agents which will penetrate the blood-brain barrier and expert central nervous actions. Annotation copyrighted by Book News, Inc., Portland, OR
Physiology Of Astroglia
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Author : Alexei Verkhratsky
language : en
Publisher: Biota Publishing
Release Date : 2015-03-01
Physiology Of Astroglia written by Alexei Verkhratsky and has been published by Biota Publishing this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-03-01 with Medical categories.
Astrocytes can be defined as the glia inhabiting the nervous system with the main function in the maintenance of nervous tissue homeostasis. Classified into several types according to their morphological appearance, many of astrocytes form a reticular structure known as astroglial syncytium, owing to their coupling via intercellular channels organized into gap junctions. Not only do astrocytes establish such homocellular contacts, but they also engage in intimate heterocellular interactions with neurons, most notably at synaptic sites. As synaptic structures house the very core of information transfer and processing in the nervous system, astroglial perisynaptic positioning assures that these glial cells can nourish neurons and establish bidirectional communication with them, functions outlined in the concepts of the astrocytic cradle and multi-partite synapse, respectively. Astrocytes possess a rich assortment of ligand receptors, ion and water channels, and ion and ligand transporters, which collectively contribute to astrocytic control of homeostasis and excitability. Astroglia control glutamate and adenosine homeostasis to exert modulatory actions affecting the real-time operation of synapses. Fluctuations of intracellular calcium can lead to the release of various chemical transmitters from astrocytes through a process termed gliotransmission. Sodium fluctuations are closely associated to those of calcium with both dynamic events interfacing signaling and metabolism. Astrocytes appear fully integrated into the brain cellular circuitry, being an indispensable part of neural networks.
Neurotransmitter Transporters
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Author : Maarten E. A. Reith
language : en
Publisher: Springer Science & Business Media
Release Date : 1996-10-01
Neurotransmitter Transporters written by Maarten E. A. Reith and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 1996-10-01 with Medical categories.
A comprehensive survey of recent advances made in characterizing neurotransmitter transporters-including their imaging in the living brain-and in elucidating the processes underlying biological transport. The expert contributors present up-to-date findings on the molecular cloning of transporters and on neurotransmitter families both in plasma membranes and in storage vesicles. They also provide essential information on the structure-activity relationships for a multitude of recently synthesized dopamine uptake blockers, on transporter changes in the context of human drug abuse, and on the role of transporters in the action of uptake blockers in vivo. The book opens the new frontier of transporters research, authoritatively presenting new insights into their roles in such diseases as brain ischemia and ALS, and into their involvement as targets for antidepressants, antiepileptics, drugs of abuse, and neurotoxins.
The Regulation Of Glial Glutamate Transporters After In Vitro Ischemic Stroke
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Author : Simran Gill
language : en
Publisher:
Release Date : 2021
The Regulation Of Glial Glutamate Transporters After In Vitro Ischemic Stroke written by Simran Gill and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with Cerebrovascular disease categories.
Stroke is the 3rd leading cause of death in the United States however it still lacks adequate treatment. Ischemic stroke is one of the major types of stroke; ischemia involves the cessation of blood flow to the brain, which is usually the result of a blood clot. Neuronal death that is observed following ischemia is primarily due to glutamatergic imbalance--an excess of glutamate release leads to excitotoxicity and subsequent cell death. The excitatory amino acid transporters (EAATs) are responsible for the regulation of extracellular glutamate, and therefore play a major role in ischemic outcomes. My project was designed to better understand the modulation of EAATs following ischemic insults, as previous studies have shown conflicting results. More specifically, we explored how EAAT activity and expression is regulated following varying severities of ischemia in glia cultures: 30-minutes, 1-hour and 2-hours of oxygen-glucose deprivation (OGD), which could be considered mild, moderate and severe ischemic insults, respectively. Furthermore, we also sought to determine the effects of Clavulanic Acid (CA), an EAAT2 expression enhancer, on EAAT expression and activity after varying ischemic insults. Previous work by our lab has found that CA provides neuroprotection after 20 minutes of OGD in neuron-glia cultures. Our study showed that with increasing length of ischemic insult, there is a decrease in glutamate transport, suggesting that these transporters are unable to effectively clear excess glutamate. This could happen via transport reversal, internalization, degradation, and/or other mechanisms. This decrease in activity is only rescued by CA pretreatment following mild ischemia. The expression of EAAT1 is downregulated after ischemia, with a more profound effect at the 1-hour time point. On the other hand, EAAT2 expression is up regulated after 30-minutes and 1-hour OGD, and decreases below control levels after 2-hours of OGD. These results suggest that these glial transporters may work together, likely as a compensatory mechanism to mitigate the increased glutamate release and decreased uptake resulting from OGD. We also found that CA significantly increased EAAT2 levels in control conditions as well as after 30-minutes of OGD, suggesting that this strategy only offers benefit in mild ischemic insults. Future studies will include cell surface biotinylation, functionality assays of Na+/K+ATPase (that provide energy for transport), and electrophysiological approaches. Additionally, studies to evaluate ubiquitination, transcription factors (such as calcineurin, which has been associated with excitotoxic cell death mechanisms), as well as the activation of mTOR-Akt-NFkB signaling cascades, and miRNAs associated with EAAT modulation, can help us further understand the mechanisms associated with EAAT regulation during ischemia. We also we investigated reactive gliosis, which can be defined by the activation of glial cells in response to a pathology. Previous work has shown that reactive gliosis is a phenotype associated with ischemia, however we wanted to define the point at which this phenomenon occurs. Our results show that reactive gliosis, which was determined by an increased expression and fluorescence of GFAP, increases with OGD insult, with a significant difference seen after 2-hours of OGD. This suggests the reactive phenotype is more prominent as the severity of ischemia increases. Future studies will include the use of more specific markers of reactive gliosis, such as BrdU as well as A1 and A2 subtype markers to take our analysis to the next step. Overall, the findings from this study helped further our knowledge regarding glutamate regulation following different severities of ischemic stroke in-vitro and could aid in the development of novel therapeutics.
Transportation Of Amino Acids And Carnitine In Neural Cell Preparations
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Author : Ritva Hannuniemi
language : en
Publisher:
Release Date : 1988
Transportation Of Amino Acids And Carnitine In Neural Cell Preparations written by Ritva Hannuniemi and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 1988 with categories.
Glutamate Related Biomarkers In Drug Development For Disorders Of The Nervous System
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Author : Institute of Medicine
language : en
Publisher: National Academies Press
Release Date : 2011-08-05
Glutamate Related Biomarkers In Drug Development For Disorders Of The Nervous System written by Institute of Medicine and has been published by National Academies Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-08-05 with Medical categories.
Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.