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Advances in Neurobiology

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https://www.readbyqxmd.com/read/27885637/the-glutamate-glutamine-cycle-in-epilepsy
#1
Tore Eid, Shaun E Gruenbaum, Roni Dhaher, Tih-Shih W Lee, Yun Zhou, Niels Christian Danbolt
Epilepsy is a complex, multifactorial disease characterized by spontaneous recurrent seizures and an increased incidence of comorbid conditions such as anxiety, depression, cognitive dysfunction, and sudden unexpected death. About 70 million people worldwide are estimated to suffer from epilepsy, and up to one-third of all people with epilepsy are expected to be refractory to current medications. Development of more effective and specific antiepileptic interventions is therefore requisite. Perturbations in the brain's glutamate-glutamine cycle, such as increased extracellular levels of glutamate, loss of astroglial glutamine synthetase, and changes in glutaminase and glutamate dehydrogenase, are frequently encountered in patients with epilepsy...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885636/glutamine-synthetase-role-in-neurological-disorders
#2
Arumugam R Jayakumar, Michael D Norenberg
Glutamine synthetase (GS) is an ATP-dependent enzyme found in most species that synthesizes glutamine from glutamate and ammonia. In brain, GS is exclusively located in astrocytes where it serves to maintain the glutamate-glutamine cycle, as well as nitrogen metabolism. Changes in the activity of GS, as well as its gene expression, along with excitotoxicity, have been identified in a number of neurological conditions. The literature describing alterations in the activation and gene expression of GS, as well as its involvement in different neurological disorders, however, is incomplete...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885635/astroglia-glutamatergic-transmission-and-psychiatric-diseases
#3
Alexei Verkhratsky, Luca Steardo, Liang Peng, Vladimir Parpura
Astrocytes are primary homeostatic cells of the central nervous system. They regulate glutamatergic transmission through the removal of glutamate from the extracellular space and by supplying neurons with glutamine. Glutamatergic transmission is generally believed to be significantly impaired in the contexts of all major neuropsychiatric diseases. In most of these neuropsychiatric diseases, astrocytes show signs of degeneration and atrophy, which is likely to be translated into reduced homeostatic capabilities...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885634/dysregulation-of-glutamate-cycling-mediates-methylmercury-induced-neurotoxicity
#4
Megan Culbreth, Michael Aschner
To examine the toxicological implications of glutamate, this chapter will focus specifically on its impact in the brain. More explicitly, it will illustrate the role glutamate plays in mediating methylmercury (MeHg)-induced neurotoxicity. In this chapter, one intends to highlight the processes that occur prior to glutamate-stimulated excitotoxicity and subsequent neurodegeneration. As such, it will emphasize three main routes by which MeHg alters glutamate homeostasis. It is essential to recognize that these effects are not mutually exclusive, and that they synergistically influence glutamate dysregulation...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885633/oligodendrocytes-development-physiology-and-glucose-metabolism
#5
Ana I Amaral, Joana M Tavares, Ursula Sonnewald, Mark R N Kotter
The glutamate-glutamine cycle is an outstanding example of how essential neuronal-glial interactions are for brain function. For several decades, this and other metabolic cycles in the brain have only included neurons and astrocytes but not oligodendrocytes, the myelinating cells of the central nervous system (CNS). Recent data revealed that oligodendrocytes are highly metabolically active cells in the brain and, therefore, should not be ignored. Using (13)C-labelled glucose in combination with nuclear magnetic resonance spectroscopy (MRS) and/or mass spectrometry (MS) it is possible to characterize metabolic functions in primary oligodendrocyte cultures...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885632/glutamine-metabolism-in-gliomas
#6
Monika Szeliga, Jan Albrecht
By histological, morphological criteria, and malignancy, brain tumors are classified by WHO into grades I (most benign) to IV (highly malignant), and gliomas are the most frequently occurring class throughout the grades. Similar to peripheral tumors, the growth of glia-derived tumor cells largely depends on glutamine (Gln), which is vividly taken up by the cells, using mostly ASCT2 and SN1 as Gln carriers. Tumor growth-promoting effects of Gln are associated with its phosphate-activated glutaminase (GA) (specifically KGA)-mediated degradation to glutamate (Glu) and/or with its entry to the energy- and intermediate metabolite-generating pathways related to the tricarboxylic acid cycle...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885631/the-glutamine-transporters-and-their-role-in-the-glutamate-gaba-glutamine-cycle
#7
Renata Leke, Arne Schousboe
Glutamine is a key amino acid in the CNS, playing an important role in the glutamate/GABA-glutamine cycle (GGC). In the GGC, glutamine is transferred from astrocytes to neurons, where it will replenish the inhibitory and excitatory neurotransmitter pools. Different transporters participate in this neural communication, i.e., the transporters responsible for glutamine efflux from astrocytes and influx into the neurons, such as the members of the SNAT, LAT, y(+)LAT, and ASC families of transporters. The SNAT family consists of the transporter isoforms SNAT3 and SNAT5 that are related to efflux from the astrocytic compartment, and SNAT1 and SNAT2 that are associated with glutamine uptake into the neuronal compartment...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885630/vesicular-glutamate-uptake
#8
Tetsufumi Ueda
Glutamate is an excitatory neurotransmitter widely used in the vertebrate central nervous systems. The synaptic transmission process is characterized by three steps: (1) presynaptic vesicular transmitter uptake, (2) presynaptic release, and (3) postsynaptic receptor activation. Presynaptic vesicular glutamate uptake plays an initial pivotal role in glutamate transmission by concentrating glutamate in the vesicular lumen prior to its release. This active glutamate transport harnesses energy derived from ATP hydrolysis, and intra- or extravesicular chloride, and is highly specific to glutamate...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885629/glutaminases
#9
Javier Márquez, José M Matés, José A Campos-Sandoval
Mammalian glutaminases catalyze the stoichiometric conversion of L-glutamine to L-glutamate and ammonium ions. In brain, glutaminase is considered the prevailing pathway for synthesis of the neurotransmitter pool of glutamate. Besides neurotransmission, the products of glutaminase reaction also fulfill crucial roles in energy and metabolic homeostasis in mammalian brain. In the last years, new functional roles for brain glutaminases are being uncovered by using functional genomic and proteomic approaches. Glutaminases may act as multifunctional proteins able to perform different tasks: the discovery of multiple transcript variants in neurons and glial cells, novel extramitochondrial localizations, and isoform-specific proteininteracting partners strongly support possible moonlighting functions for these proteins...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885628/bcaa-metabolism-and-nh3-homeostasis
#10
M E Conway, S M Hutson
The branched chain amino acids (BCAA) are essential amino acids required not only for growth and development, but also as nutrient signals and as nitrogen donors to neurotransmitter synthesis and glutamate/glutamine cycling. Transamination and oxidative decarboxylation of the BCAAs are catalysed by the branched-chain aminotransferase proteins (BCATm, mitochondrial and BCATc, cytosolic) and the branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC), respectively. These proteins show tissue, cell compartmentation, and protein-protein interactions, which call for substrate shuttling or channelling and nitrogen transfer for oxidation to occur...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885627/enzyme-complexes-important-for-the-glutamate-glutamine-cycle
#11
Mary C McKenna, Gustavo C Ferreira
Transient multienzyme and/or multiprotein complexes (metabolons) direct substrates toward specific pathways and can significantly influence the metabolism of glutamate and glutamine in the brain. Glutamate is the primary excitatory neurotransmitter in brain. This neurotransmitter has essential roles in normal brain function including learning and memory. Metabolism of glutamate involves the coordinated activity of astrocytes and neurons and high affinity transporter proteins that are selectively distributed on these cells...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885626/anaplerosis-for-glutamate-synthesis-in-the-neonate-and-in-adulthood
#12
Eva Brekke, Tora Sund Morken, Anne B Walls, Helle Waagepetersen, Arne Schousboe, Ursula Sonnewald
A central task of the tricarboxylic acid (TCA, Krebs, citric acid) cycle in brain is to provide precursors for biosynthesis of glutamate, GABA, aspartate and glutamine. Three of these amino acids are the partners in the intricate interaction between astrocytes and neurons and form the so-called glutamine-glutamate (GABA) cycle. The ketoacids α-ketoglutarate and oxaloacetate are removed from the cycle for this process. When something is removed from the TCA cycle it must be replaced to permit the continued function of this essential pathway, a process termed anaplerosis...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885625/glucose-lactate-%C3%AE-hydroxybutyrate-acetate-gaba-and-succinate-as-substrates-for-synthesis-of-glutamate-and-gaba-in-the-glutamine-glutamate-gaba-cycle
#13
Leif Hertz, Douglas L Rothman
The glutamine-glutamate/GABA cycle is an astrocytic-neuronal pathway transferring precursors for transmitter glutamate and GABA from astrocytes to neurons. In addition, the cycle carries released transmitter back to astrocytes, where a minor fraction (~25 %) is degraded (requiring a similar amount of resynthesis) and the remainder returned to the neurons for reuse. The flux in the cycle is intense, amounting to the same value as neuronal glucose utilization rate or 75-80 % of total cortical glucose consumption...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885624/introduction-to-the-glutamate-glutamine-cycle
#14
Ursula Sonnewald, Arne Schousboe
The term 'glutamate-glutamine cycle' was coined several decades ago based on the observation that using certain (14)C-labeled precursors for studies of brain metabolism the specific radioactivity of glutamine generated from glutamate was higher than that of glutamate, its immediate precursor. This is metabolically impossible unless it is assumed that at least two distinct pools of these amino acids exist. This combined with the finding that the enzyme synthesizing glutamine from glutamate was expressed in astrocytes but not in neurons formed the basis of the notion that a cycle must exist in which glutamate released from neurons is transported into astrocytes, converted to glutamine which is subsequently returned to neurons and converted to glutamate by an enzyme the activity of which is much higher in neurons than in astrocytes...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27848232/erratum
#15
M Mohamed Essa, Mohammed Akbar, Gilles Guillemin
No abstract text is available yet for this article.
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27651267/plant-derived-natural-products-for-parkinson-s-disease-therapy
#16
T Sengupta, J Vinayagam, R Singh, P Jaisankar, K P Mohanakumar
Plant-derived natural products have made their own niche in the treatment of neurological diseases since time immemorial. Parkinson's disease (PD), the second most prevalent neurodegenerative disorder, has no cure and the treatment available currently is symptomatic. This chapter thoughtfully and objectively assesses the scientific basis that supports the increasing use of these plant-derived natural products for the treatment of this chronic and progressive disorder. Proper considerations are made on the chemical nature, sources, preclinical tests and their validity, and mechanisms of behavioural or biochemical recovery observed following treatment with various plants derived natural products relevant to PD therapy...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27651266/modulatory-effects-of-dietary-amino-acids-on-neurodegenerative-diseases
#17
Senthilkumar Rajagopal, Supraj Raja Sangam, Shubham Singh, Venkateswara Rao Joginapally
Proteins are playing a vital role in maintaining the cellular integrity and function, as well as for brain cells. Protein intake and supplementation of individual amino acids can affect the brain functioning and mental health, and many of the neurotransmitters in the brain are made from amino acids. The amino acid supplementation has been found to reduce symptoms, as they are converted into neurotransmitters which in turn extenuate the mental disorders. The biosynthesis of amino acids in the brain is regulated by the concentration of amino acids in plasma...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27651265/choline-and-the-brain-an-epigenetic-perspective
#18
Rola Aldana Bekdash
Choline is an essential nutrient that is required for normal development of the brain. Via its metabolite betaine, it participates in the synthesis of S-adenosylmethionine, a major methyl donor for histone and DNA methylation, two epigenetic mechanisms that regulate gene expression and may alter brain function. Besides its role in methyl group metabolism, choline also has pivotal functions, including the maintenance of structural integrity of membranes and modulation of cholinergic neurotransmission, functions that are often dysregulated in some neurodegenerative disorders...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27651264/role-of-polyunsaturated-fatty-acids-and-their-metabolites-on-stem-cell-proliferation-and-differentiation
#19
Mohammad Abdur Rashid, Mahmuda Haque, Mohammed Akbar
The nervous system is highly enriched with long-chain polyunsaturated fatty acids (PUFAs). Essential fatty acids, namely, ω-6 (n - 6) and ω-3 (n - 3) PUFA, and their metabolites are critical components of cell structure and function and could therefore influence stem cell fate. The available supporting experimental data reveal that n - 6 and n - 3 PUFA and their metabolites can act through multiple mechanisms to promote the proliferation and differentiation of various stem cell types. PUFAs and their mediators regulate several processes within the brain, such as neurotransmission, cell survival and neuroinflammation, and thereby mood and cognition...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27651263/detoxification-of-carbonyl-compounds-by-carbonyl-reductase-in-neurodegeneration
#20
Mohammad Abdur Rashid, Mahmuda Haque, Mohammed Akbar
Oxidative stress in the brain is the major cause of neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's, and Creutzfeldt-Jakob diseases or amyotrophic lateral sclerosis. Under conditions of oxidative stress, the production of highly reactive oxygen species (ROS) overwhelms antioxidant defenses, resulting in the modification of macromolecules and their deposition in neuronal cell tissues. ROS plays an important role in neuronal cell death that they generate reactive aldehydes from membrane lipid peroxidation...
2016: Advances in Neurobiology
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