TY - JOUR. T1 - Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro. AU - Cunningham, Mark O.. AU - Woodhall, Gavin L.. AU - Thompson, Sarah E.. AU - Dooley, David J.. AU - Jones, Roland S G. PY - 2004/9/6. Y1 - 2004/9/6. N2 - We have recently shown that the anticonvulsant drugs phenytoin, lamotrigine and sodium valproate all reduce the release of glutamate at synapses in the entorhinal cortex in vitro. In the present investigation we determined whether this property was shared by gabapentin and pregabalin, using whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) in layer V neurons in slices of rat entorhinal cortex. Both drugs reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation of afferent inputs, suggesting a presynaptic effect to reduce glutamate release. The frequency of spontaneous EPSCs (sEPSCs) was concurrently reduced by GBP, further supporting a presynaptic action. ...

TY - JOUR. T1 - The role of glutamate transporters in glutamate homeostasis in the brain. AU - Takahashi, Michiko. AU - Billups, Brian. AU - Rossi, David. AU - Sarantis, Monique. AU - Hamann, Martine. AU - Attwell, David. PY - 1997/1. Y1 - 1997/1. N2 - Glutamate transporters in neurones and glia, four of which have been cloned from mammals, play a crucial rule in controlling the extracellular glutamate concentration in the brain. In normal conditions, they remove glutamate from the extracellular space and thereby help to terminate glutamatergic synaptic transmission and to prevent the extracellular glutamate concentration from rising to neurotoxic values. Glutamate transport on these carriers is thought to be driven by the cotransport of Na+, the countertransport of K+, and either the cotransport of H+ or the counter-transport of OH-. Activating the transporters also activates an anion conductance in their structure, the anion flux through which is not coupled to glutamate movement and varies ...

A new study suggests a role for brain imaging in the assessment and potential treatment of chronic pain.. University of Michigan researchers are the first to use brain imaging procedures to track the clinical action of pregabalin, a drug that is prescribed to patients suffering from fibromyalgia and neuropathic pain.. Three different brain imaging procedures were performed - proton magnetic resonance spectroscopy, functional magnetic resonance imaging and functional connectivity magnetic resonance imaging - in 17 patients with fibromyalgia.. Fibromyalgia is a chronic pain disorder thought to result from a disturbance in the way the central nervous system processes pain. It affects an estimated 3 to 6 percent of the world population.. Previous research has shown that fibromyalgia patients may have heightened neural activity in the insula, and that this excess activity may be related to elevated levels of the excitatory neurotransmitter glutamate. Brain imaging in the current study suggests ...

Evidence that a catalytic glutamate and an Arginine Toggle act in concert to mediate ATP hydrolysis and mechanochemical coupling in a viral DNA packaging motor.

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Synaptic transmission at glutamatergic synapses mediates and regulates basically all aspects of brain functions. The strength of these synapses is subjected to potentiation and depression and these plastic modifications are plausible candidates for information storage in the brain. Excessive activity at glutamatergic synapses, namely excitotoxicity, occurs in many brain diseases and is a critical factor for neuronal death or degeneration. Therefore, to elucidate the molecular mechanisms underlying glutamatergic transmission, plasticity and excitotoxicity constitutes the first step to understand neuronal information processing, learning, memory and brain diseases.; In my dissertation, I report the results of three independent but closely related studies on synaptic transmission, plasticity and excitotoxicity, respectively. In the first part, I provide evidence that two different glutamate transporters, one ...

Glutamate has been shown to lead to neurotoxicity and subsequent neurodegeneration through changes in synaptic function, loss of glutamatergic neurons, synapses, and dendrites. All of these characteristics are also observed during aging or in age-associated neurodegenerative diseases. To probe the effects of excess glutamate and determine if these effects might contribute to the morphological and functional changes associated with aging, our laboratory generated a transgenic mouse model that over-expresses the mitochondrial glutamate dehydrogenase 1 (GLUD1) gene. This transgene was only expressed in neurons through the use of the neuron-specific enolase promoter. The Glud1 Tg mouse model generated in our laboratory demonstrated significantly increased GLUD1 levels, GLUD activity, extracellular glutamate levels, and increased glutamate release after stimulation as compared to wild type (wt). There were also many significant morphological changes observed in the Tg mice including cell layer ...

L-glutamate (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system. Monitoring extracellular Glu is critical to understanding Glu regulation to discriminate physiological and pathological roles. To overcome the limitations of previous in vivo extracellular Glu studies, we developed Glu selective microelectrode arrays with better spatial and temporal resolutions than commonly used techniques like microdialysis. We used these microelectrode arrays to characterize basal and potassium-evoked Glu neurotransmission in the normal rat brain. We then investigated disease-related Glu alterations in a rat model of Parkinsons disease and normal Glu regulation in young and aged rhesus monkeys. In the normal anesthetized rat striatum and frontal cortex, basal Glu was regulated by active release and uptake mechanisms, fully TTX-dependent, and measured at ~2 micromolar levels. Potassium-evoked Glu kinetics were fast, concentration-dependent, and rapidly reproducible at 15-20 seconds

Excitotoxicity can occur from substances produced within the body (endogenous excitotoxins). Glutamate is a prime example of an excitotoxin in the brain, and it is also the major excitatory neurotransmitter in the mammalian CNS.[10] During normal conditions, glutamate concentration can be increased up to 1mM in the synaptic cleft, which is rapidly decreased in the lapse of milliseconds.[11] When the glutamate concentration around the synaptic cleft cannot be decreased or reaches higher levels, the neuron kills itself by a process called apoptosis.[12][13]. This pathologic phenomenon can also occur after brain injury and spinal cord injury. Within minutes after spinal cord injury, damaged neural cells within the lesion site spill glutamate into the extracellular space where glutamate can stimulate presynaptic glutamate receptors to enhance the release of additional glutamate.[14] Brain trauma or stroke can cause ischemia, in which blood flow is reduced to inadequate levels. Ischemia is followed ...

MSG is used to give a meaty, savory, or brothy taste to foods by stimulating the glutamate receptors on the tongue. There are glutamate receptors in other parts of the body, notably the brain, where glutamate is a neurotransmitter. Glutamates can be produced by fermentation of starches or sugars, but also by breaking the bonds between amino acids in proteins, leaving free amino acids. This process is done by heat or by enzymes, and is called hydrolyzing because the bonds are broken by adding water. When proteins are broken down into their constituent amino acids, the result can contain as much as 20 percent glutamates. This is why hydrolyzed vegetable protein is often listed as an ingredient in foods, to give them a meaty or savory flavor. There is evidence that some people are sensitive to free glutamates, and may get headaches or other symptoms if too much is ingested. This may be related to pyridoxine (vitamin B6) deficiencies, as this vitamin is necessary for glutamate metabolism. ...

It is generally accepted that increased glutamatergic activity, resulting from the elevated extracellular glutamate which occurs in the brain during an ischaemic episode (Benveniste et al., 1984; Baldwin et al., 1994; Lee et al., 1999), is a crucial initiating event, leading to cell death (see Szatkowski & Attwell, 1994; Kristián & Siesjö, 1998; Green et al., 2000). It has previously been reported that exposing cerebral tissue to ischaemic conditions in vitro can induce glutamate release and this has been demonstrated using cerebral tissue from both rat (Taylor et al., 1995; Roettger & Lipton, 1996; Saransaari & Oja, 1997) and human (Hegstad et al., 1996). The results from the current study confirmed these findings in prisms of rat cortex, simulating ischaemia by use of a hypoxic medium, with no added glucose. Cortical tissue was used in the current study because this region is severely compromized by occlusion of the middle cerebral artery (MCA) in vivo both in animals and humans (e.g. ...

The protective enzymes in a babys brain are still immature, and therefore are unable to effectively detoxify the excitotoxins that enter its brain. This would mean that in the case of a pregnant woman eating meals high in excitotoxin taste enhancers, the baby could be exposed to these high glutamate levels for many hours. It is not unreasonable to assume that mothers will eat several meals and snacks containing various forms of excitotoxins such as MSG, hydrolyzed vegetable protein, and aspartame. This could produce a high concentration of glutamate exposure in the babys brain several times a day. Also significant is the fact that the immature brain is four times more sensitive to the damaging effects of excitotoxins than the adult brain. Thus, following a dose of MSG, the babys blood level of glutamate may remain high for many hours. Since no experimental work can be done on pregnant women or children, we must look to animal research studies for some clues. In a study with mice and rats ...

Antibodies were raised against two distinct extracellular sequences of the rat mGluR1 metabotropic glutamate receptor expressed as bacterial fusion proteins. Both antibodies specifically reacted with mGluR1 in the rat cerebellum and inhibited the mGluR1 activity as assessed by the analysis of glutamate-stimulated inositol phosphate formation in CHO cells expressing mGluR1. Using these antibodies, we examined the role of mGluR1 in the induction of long-term depression in cultured Purkinje cells. In voltage- clamped Purkinje cells, current induced by iontophoretically applied glutamate was persistently depressed by depolarization of the Purkinje cells in conjunction with the glutamate application. The mGluR1 antibodies completely blocked the depression of glutamate-induced current. The results indicate that activation of mGluR1 is necessary for the induction of cerebellar long-term depression and that these mGluR1 antibodies can be used as selective antagonists ...

In this article, David Nicholls and David Attwell describe recent advances in our understanding of the mechanisms by which excitatory amino acids are released from cells, and of the way in which a low extracellular glutamate concentration is maintained. Glutamate can be released from cells by two me …

Glutamate is the major excitatory neurotransmitter in humans. There have been studies to suggest that nicotine increases glutamate release by attaching to the core neurons of the brains reward system, speeding up the release of dopamine (a neurotransmitter that plays a major role in the motivational component of reward-motivated behaviour) and preventing GABA, another neurotransmitter that produces a calming effect, from slowing down dopamine release. In smoking, this effect causes a person to crave nicotine - the addictive component of cigarette smoke - perpetuating the cycle ...

Abstract Immunoinflammatory‐mediated demyelination, the main pathological feature of multiple sclerosis (MS), is regularly accompanied by neurodegenerative processes, mostly in the form of axonal degeneration, which could be initiated by glutamate excitotoxicity. In the current study, the relationship between Th17‐mediated inflammatory and excitotoxic events was investigated during an active phase of MS. Cerebrospinal fluid (CSF) of patients with MS and control subjects was collected, and IL‐17A and glutamate levels were determined. IL‐17A level was significantly higher in patients with MS; whereas no statistically significant changes in glutamate concentrations were found. There was a direct correlation between IL‐17A and glutamate levels; IL‐17A levels were also associated wi...

Ghreli n (Ghr) is a peptide that participates i n the modulatio n of several biological processes. Ghr admi nistratio n i nto the hippocampus improves lear ni ng a nd memory i n differe nt memory test

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system, and in addition to its central role in fast excitatory signaling it is also involved in synaptogenesis, synaptic plasticity, and the pathogenesis of certain neurologic diseases. Although glutamate acts as a neurotransmitter in all pathways of the central nervous system, the response to glutamate is not uniform at all glutamatergic synapses and varies with the type of glutamate receptor expressed on the postsynaptic membrane. In this context, we are interested in studying synapse-specific expression of postsynaptic NMDA and metabotropic glutamate receptors. My laboratory characterizes the molecular mechanisms underlying neurotransmitter receptor transport and localization at the synapse using several research strategies which include (1) defining sorting motifs present in neurotransmitter receptor cytosolic domains, (2) isolating neurotransmitter receptor-associated proteins, and (3) determining the role ...

PMID: 31545255 Open Access Sabogal-Guaqueta AM, Hobbie F, Keerthi A, Oun A, Kortholt A, Boddeke E, Dolga A (2019) Biomed Pharmacother Abstract: Mitochondrial dysfunction and inflammation contribute to the initiation and development of several brain pathological conditions, including Alzheimers disease and cerebral ischemia. Linalool is an aromatic plant-derived monoterpene alcohol with reported anti-inflammatory, and anti-oxidant properties. We investigated the role of linalool on glutamate-induced mitochondrial oxidative stress in immortalized neuronal HT-22 cells. Glutamate induced oxidative stress in neuronal cells, as detected by real-time cell impedance measurements, MTT assay, and analysis of Annexin V/PI. Administration of linalool 100 μM reduced cell death mediated by glutamate. Staining of glutamate-stimulated mitochondria by MitoTracker revealed improved morphology in the presence of linalool. Furthermore, we demonstrated a potential neuroprotective effect of linalool in conditions ...

FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Several transcript variants encoding different isoforms have been found for this gene. ...

NMDA receptors is a very touchy and controversial area. On one hand, NMDA activity is responsible for memory and learning. On the other hand, overstimulation of NMDA receptors causes seizures and neuron death (neurotoxicity). Glutamate is the main excitatory neurotransmitter that agonizes these receptors. Anything that reduces NMDA activity either through blocking them or through reducing glutamate has been called neuroprotective. Neuroprotection has been the focus of biomed therapies for autism. There are several theories why neuroprotection is needed for autism. First, many autistic children have abnormal EEG activity or seizures, which affect learning and language. Second, high glutamate and overstimulation of NMDA receptors is often a result of brain inflammation (encephalopathy), which is now a leading theory of autism causes. So, it is hard to debate that NMDA receptors must be protected from overstimualtion. Especially in my sons case because he had abnormal EEG until we started him on ...

During the verbal fluency task, subjects with an ARMS showed greater activation than did controls in the middle frontal gyrus bilaterally. Thalamic glutamate levels were lower in the ARMS group than in control group. Within the ARMS group, thalamic glutamate levels were negatively associated with activation in the right dorsolateral prefrontal and left orbitofrontal cortex, but positively associated with activation in the right hippocampus and in the temporal cortex bilaterally. There was also a significant group difference in the relationship between cortical activation and thalamic glutamate levels, with the control group showing correlations in the opposite direction to those in the ARMS group in the prefrontal cortex and in the right hippocampus and superior temporal gyrus ...

Excluding, it is right away known that the highest suscepti- bility to the glutamate-mediated excitotoxicity is observed in (1) mammalian male neonates in comparison to the adults, females, and other vertebrates (Garattini 1979); (2) in cerebral regions where glutamate receptors density is lofty such as hip- pocampus (Meldrum 1993b; Beas-Zarate et al. As a result, it is respected to procure improvement assessments from perfect tissues, when viable, to allocate for the benefit of the measurement of hallucinogenic extermination to the homogeniza- tion and separation procedures. When it comes to serving conservation, Dr [url=http://thewelcomecentre.org/documents/practice24/mode12/]cheap careprost 3 ml on line[/url] symptoms stomach flu. While this propose to accumulates more than 150 rows of figures per business on av- erage, they can normally be against without much repair, e. Schapranow and Franziska H?ger physicians require a holistic view on all relevant diligent specifics when making treatment ...

Dr. Graham L. Collingridge accepted the invitation on 18 March 2007 (self-imposed deadline: 18 June 2007). This article will briefly cover: The discovery of the NMDA receptor, its unusual properties (Mg block, slow kinetics, Ca permeability, voltage-dependence, glycine co-agonist site), its role in synaptic transmission, synaptic plasticity and diseases. The NMDA receptor is one of the four major classes of receptors that respond to L-glutamate, the major excitatory neurotransmitter in the brain. It is named after the synthetic chemical N-methyl-D-aspartate, which is a highly selective agonist for this receptor. THe NMDA receptor (NMDAR) has unique properties that distinguishes it from the other three major glutamate receptor classes - AMPA receptors, kainate receptors and metabotropic receptors. The NMDAR is a tetramer, which is made up from various combinations of the subunits NR1, NR2A, NR2B, NR2C, NR2D, NR3A and NR3B. Most NMDARs contain 2 NR1 subunits, which bind the co-agonist glycine and ...

Glutamate is the major excitatory neurotransmitter in the central nervous system. The family of glutamate receptors play a critical role in synaptic plasticity and learning and memory. We are interested in understanding the roles of glutamate receptors and in particular N-methyl-D-aspartate (NMDA) and glutamate delta receptors in the central nervous system. The eventual goal is apply this undestanding to develop therpeuatics to treat severe neuropsychiatric and neurological disorders ...

Microglia are resident immune cells in the CNS and the literature has confirmed that they have a macrophage-like phenotype, with regard to morphological and quantitative changes during microglial cell activation (5). Microglia form one of the main factors in the occurrence and development of neuroinflammation (19). Undifferentiated, resting microglia are responsible for monitoring and patrolling the brain environment, as well as activating a response to injury and infection (20). Activated microglia trigger the inflammatory immune response in the nervous system by releasing cytokines, including IL-1, IL-6 and TNF-α, which clears damaged and necrotic cells or neurons from the lesion (21). However, when microglial cells remain activated, they secrete a large number of neurotoxic mediators, including inflammatory cytokines, inflammatory chemokines, ROS, NO and the excitotoxic amino acid glutamate, which disrupt synapses and neural connections in the brain, triggering a series of neuroinflammatory ...

One very important subset of synapses are capable of forming memory traces by means of long-lasting activity-dependent changes in synaptic strength.[39] The best-known form of neural memory is a process called long-term potentiation (abbreviated LTP), which operates at synapses that use the neurotransmitter glutamate acting on a special type of receptor known as the NMDA receptor.[40] The NMDA receptor has an associative property: if the two cells involved in the synapse are both activated at approximately the same time, a channel opens that permits calcium to flow into the target cell.[41] The calcium entry initiates a second messenger cascade that ultimately leads to an increase in the number of glutamate receptors in the target cell, thereby increasing the effective strength of the synapse. This change in strength can last for weeks or longer. Since the discovery of LTP in 1973, many other types of synaptic memory traces have been found, involving increases or decreases in synaptic strength ...

One very important subset of synapses are capable of forming memory traces by means of long-lasting activity-dependent changes in synaptic strength.[39] The best-known form of neural memory is a process called long-term potentiation (abbreviated LTP), which operates at synapses that use the neurotransmitter glutamate acting on a special type of receptor known as the NMDA receptor.[40] The NMDA receptor has an associative property: if the two cells involved in the synapse are both activated at approximately the same time, a channel opens that permits calcium to flow into the target cell.[41] The calcium entry initiates a second messenger cascade that ultimately leads to an increase in the number of glutamate receptors in the target cell, thereby increasing the effective strength of the synapse. This change in strength can last for weeks or longer. Since the discovery of LTP in 1973, many other types of synaptic memory traces have been found, involving increases or decreases in synaptic strength ...

CAG codon in the gene codes for amino acid glutamate, which is an essential neurotransmitter in the brain, that conveys information from neuron to another neuron.. Why not all DNA are the same and why your DNA is unique?. DNA in every human beings are not the same and there is something in it that makes you totally unique; and that is known as the Single nucleotide polymorphism. Single nucleotide polymorphism is also known as SNP, is variation in a genetic sequence that affects only one of the basic building blocks like adenine, guanine , thymin or cytosine in a segment of a DNA. SNP exists in more than 1 percent of a population in the world. Around 335 million SNP have been discovered in human genome till now.. For example:. SNP is the substitution of a cytosine (C) for a guanine (G) in the nucleotide sequence AACGAT, thereby producing the sequence AACCAT. If AACGAT coded for one particular enzyme or protein, the substituted SNP AACCAT will code for another enzyme or protein. This entirely ...

Glutathione is a very small protein composed of only three amino acids (Glutamate, Glycine, and Cysteine). It is an important antioxidant in plants, animals, fungi, and some bacteria and archaea, preventing damage to important cellular components cau

L-(+)-Glutamic acid hydrochloride 138-15-8 MSDS report, L-(+)-Glutamic acid hydrochloride MSDS safety technical specifications search, L-(+)-Glutamic acid hydrochloride safety information specifications ect.

We study the properties of these glutamate transporters in expression systems as well as in acute tissue, such as the hippocampus and cerebellum. Glutamate transporters harness the energy stored in the electrochemical gradients for Na+, H+, and K+ to force glutamate into cells against its concentration gradient. Because transport is electrogenic, we can monitor transporter activity using electrophysiological (patch-clamp) techniques. To provide insight into the intrinsic properties of these transporters, we apply glutamate with sub-millisecond resolution to outside-out patches using a piezoelectric bimorph. These studies are combined with whole-cell recordings from visually-identified astrocytes and neurons in acute brain slices to monitor the activity of transporters during synaptic transmission. Through these studies we hope to determine the fate of glutamate after it is released - how far it diffuses, the types and locations of the receptors it activates, and the role of transporters in ...

How much of Glutamic acid, Glu or E, proteinogenic amino acid is present in Pork, fresh, loin, whole, separable lean only, cooked, braised in details, quantity how high or low Glutamic acid, Glu or E, proteinogenic amino acid nutrient content it has.

Click to launch & play an online audio visual presentation by Prof. Vladimir Parpura on Mechanisms of glutamate release from astrocytes, part of a collection of online lectures.

Here you can read about Uses, Benefits, Sources and Dosage of Glutamic Acid. Glutamic acid is considered as the essential amino acid for the protein synthesis.

Principal Investigator：AKAIKE Akinori, Project Period (FY)：1997 - 1998, Research Category：Grant-in-Aid for Scientific Research (B), Section：一般, Research Field：Biological pharmacy

While the cause of amyotrophic lateral sclerosis, or ALS, remains a mystery, many researchers are trying to develop a cure by stopping its effect---the dea

Glutamic acid Name L-Glutamic acid Molecular Weight 147.12926 g/mol Molecular Formula XLogP -3.3 CAS No. 56-86-0m.p.205℃pK1(25℃)2.10pK2(25℃)9.47pKR(25℃)4.07 Links * Amino acid * Acidic amino acid * Aspartic acid * Glutamic acid *

AGO CLIP Reveals an Activated Network for Acute Regulation of Brain Glutamate Homeostasis in Ischemic Stroke …………… Kobayashi M, Benakis C, Anderson C, Moore MJ, Poon C, Uekawa K, Dyke JP, Fak JJ, Mele A, Park CY, Zhou P, Anrather J, Iadecola C, Darnell RB. Cell Rep. 2019 Jul 23;28(4):979-991.e6. PubMed 00. ...

(gloo-TA-mik A-sid) One of twenty amino acids (molecules that join together to form proteins). Glutamic acid may help nerve cells send and receive information from other cells. It is being studied for its ability to decrease or prevent nerve damage caused by anticancer drugs. Also called L-glutamic acid.

Such any conclusion is contract with prior scientific studies showing which eCBs work as retrograde messengers in glutamate synapses of putative Doctor 5-HT neurons (Haj-Dahmane & Shen, June 2006, 09).

Pahner, I.; Hoeltje, M.; Winter, S.; Takamori, S.; Bellocchio, E. E.; Spicher, K.; Laake, P.; Nuernberg, B.; Ottersen, O. P.; Ahnert-Hilger, G.: Functional G-protein heterotrimers are associated with vesicles of putative glutamatergic terminals: implications for regulation of transmitter uptake (vol 23, pg 398, 2003). Molecular and Cellular Neuroscience 24 (3), p. 850 - 850 (2003 ...

When we want to understand the diverse world of our body which is controlled by our brain, we need to know about neurotransmission.

TY - JOUR. T1 - Comparison of excitatory currents activated by different transmitters on crustacean muscle. T2 - II. Glutamate-activated currents and comparison with acetylcholine currents present on the same muscle. AU - Lingle, Chris. AU - Auerbach, Anthony. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 1983/4/1. Y1 - 1983/4/1. N2 - The properties of glutamate-activated excitatory currents on the gm6 muscle from the foregut of the spiny lobsters Panulirus argus and interruptus and the crab Cancer borealis were examined using either noise analysis, analysis of synaptic current decays, or slow iontophoretic currents. The properties of acetylcholine currents activated in nonjunctional regions of the gm6 muscle were also examined. At 12°C and -80 mV, the predominant time constant of power spectra from glutamate-activated current noise was ~7 ms and the elementary conductance was ~34 pS. At 12°C and -80 mV, the predominant time constant of acetylcholine-activated ...

The aim of this thesis is to better understand the regulation of the cystine/glutamate antiporter (system xc-) and its role in regulating neuronal survival and death. Expressed primarily on astrocytes, system xc- takes up cystine and releases glutamate in a 1:1 ratio. Cystine uptake is the rate-limiting step in glutathione synthesis, the brains main antioxidant. Glutamate released into the extrasynaptic space can regulate neuronal function; however excessive glutamate release can cause excitotoxicity. The dual actions of system xc- make it of interest in many neurodegenerative diseases where oxidative stress and excitotoxicity are involved. We investigated the regulation of system xc- in SOD1-G93A transgenic mouse model of ALS. We observed an increase in cystine uptake and glutamate release through system xc- in spinal cord slices of SOD1-G93A transgenic mice. We did not observe a change in the function of the main glutamate clearance transporter, excitatory amino acid transporter (EAAT). This

The aims of this study were twofold: (i) to determine quantitatively the contribution of glutamate/glutamine cycling to total astrocyte/neuron substrate trafficking for the replenishment of neurotransmitter glutamate; and (ii) to determine the relative contributions of anaplerotic flux and glutamate/glutamine cycling to total glutamine synthesis. In this work in vivo and in vitro (13)C NMR spectroscopy were used, with a [2-(13)C]glucose or [5-(13)C]glucose infusion, to determine the rates of glutamate/glutamine cycling, de novo glutamine synthesis via anaplerosis, and the neuronal and astrocytic tricarboxylic acid cycles in the rat cerebral cortex. The rate of glutamate/glutamine cycling measured in this study is compared with that determined from re-analysis of (13)C NMR data acquired during a [1-(13)C]glucose infusion. The excellent agreement between these rates supports the hypothesis that glutamate/glutamine cycling is a major metabolic flux ( approximately 0.20 micromol/min/g) in the cerebral

An amino acid neurotransmitter is an amino acid which is able to transmit a nerve message across a synapse. Neurotransmitters (chemicals) are packaged into vesicles that cluster beneath the axon terminal membrane on the presynaptic side of a synapse in a process called endocytosis.[1]. Amino acid neurotransmitter release (exocytosis) is dependent upon calcium Ca2+ and is a presynaptic response. There are inhibitory amino acids (IAA) or excitatory amino acids (EAA). Some EAA are L-Glutamate, L-Aspartate, L-Cysteine, and L-Homocysteine.[2] These neurotransmitter systems will activate post-synaptic cells.[3] Some IAA include GABA, Glycine, β-Alanine, and Taurine.[2] The IAA depress the activity of post-synaptic cells.[3]. ...

Traumatic brain injury (TBI) is a common neurosurgical problem with a high morbidity and mortality. Studies interested in defining possible therapeutic targets in TBI have led to an appreciation of two phases of injury. These phases are referred to as primary and secondary TBI. The primary injury encompasses the immediate insult, diffuse axonal injury, hemorrhage, contusion, and primary ischemia. The secondary injury evolves over the post-traumatic period and is due to a combination of vasogenic and cytotoxic edema resulting from several processes including; glutamate excitotoxicity, disturbance of ionic homeostasis, lipid peroxidation, generation of nitric oxide (NO) and free radicals, and release of inflammatory regulators such as bradykinin and eicosanoids. It has long been recognized that one of the most important factors in the secondary injury process is the indiscriminate release of the excitatory neurotransmitter glutamate from neurons and glia. Glutamate excitotoxicity leads to ...

Recent evidence suggests that Alzheimers disease (AD) and depression share common mechanisms of pathogenesis. In particular, deregulation of glutamate-mediated excitatory signaling may play a role in brain dysfunction in both AD and depression. We have investigated levels of glutamate and its precursor glutamine in the cerebrospinal fluid (CSF) of patients with a diagnosis of probable AD or major depression compared to healthy controls and patients with hydrocephalus. Patients with probable AD or major depression showed significantly increased CSF levels of glutamate and glutamine compared to healthy controls or hydrocephalus patients. Furthermore, CSF glutamate and glutamine levels were inversely correlated to the amyloid tau index, a biomarker for AD. Results suggest that glutamate and glutamine should be further explored as potential CSF biomarkers for AD and depression.

TY - JOUR. T1 - Glutamatergic afferents of the ventral tegmental area in the rat. AU - Geisler, Stefanie. AU - Derst, Christian. AU - Veh, Rüdiger W.. AU - Zahm, Daniel S.. PY - 2007/5/23. Y1 - 2007/5/23. N2 - Glutamatergic inputs to the ventral tegmental area (VTA), thought crucial to the capacity of the VTA to detect and signal stimulus salience, have been reported to arise in but a few structures. However, the afferent system of the VTA comprises very abundant neurons within a large formation extending from the prefrontal cortex to the caudal brainstem. Neurons in nearly all parts of this continuum may be glutamatergic and equivalently important to VTA function. Thus, we sought to identify the full range of glutamatergic inputs to the VTA by combining retrograde transport of wheat germ agglutinin-bound gold after injections into the VTA with nonisotopic in situ hybridization of the vesicular glutamate transporters (VGLUTs) 1, 2, and 3. We found glutamatergic neurons innervating the VTA in ...

Dive into the research topics of Mobility of NMDA autoreceptors but not postsynaptic receptors at glutamate synapses in the rat entorhinal cortex. Together they form a unique fingerprint. ...

Glutamate is the primary excitatory neurotransmitter in the mammalian central nervous system. The precise control of extracellular glutamate is crucial for the maintenance of normal synaptic transmission and the prevention of excitotoxicity. High-affinity glutamate transporters ensure termination of glutamatergic neurotransmission and keep the synaptic glutamate concentration below excitotoxic levels. In layer III, a region that is especially prone to cell damage in Alzheimers disease, schizophrenia and epilepsy, and layer V of the medial entorhinal cortex (mEC) effects of blocking glutamate uptake on excitatory synaptic transmission were studied. Extracellular recordings in rat brain slices revealed that application of glutamate uptake inhibitors significantly reduced stimulus-induced negative field potentials in both, layer III and V of the mEC. This effect showed no significant differences in both layers suggesting a similar glutamate regulation in layer III and V. Therefore, only layer III ...

The glutamate transporter GLT-1 is crucial for the maintenance of low interstitial glutamate concentrations. by disrupting the association between Hsp90 and GLT-1. Utilizing a style of TLE, we showed that long-term systemic administration of 17AAG significantly suppressed spontaneous repeated seizures and ameliorated astrogliosis. General, these results claim that up-regulation of GLT-1 by inhibiting Hsp90 in reactive astrocytes could be a potential healing focus on for the treating epilepsy and excitotoxicity. Launch Epilepsy is among the most common chronic neurological illnesses, yet around one-third of affected sufferers do not react to anticonvulsive medications PFI-3 supplier that focus on neurons (Kwan et al., 2011). Latest studies claim that astrocytes certainly are a potential focus on for the healing treatment of intractable epilepsy (Hja, 2014; Robel et al., 2015). GLT-1 (EAAT2; slc1a2) is normally predominantly portrayed in astrocytes and in charge of maintaining low extracellular ...

Glutamine and glutamate are known to play important roles in cancer biology. However, no detailed information is available in terms of their levels of involvement in various biological processes across different cancer types, whereas such knowledge could be critical for understanding the distinct characteristics of different cancer types. Our computational study aimed to examine the functional roles of glutamine and glutamate across different cancer types. We conducted a comparative analysis of gene expression data of cancer tissues versus normal control tissues of 11 cancer types to understand glutamine and glutamate metabolisms in cancer. Specifically, we developed a linear regression model to assess differential contributions by glutamine and/or glutamate to each of seven biological processes in cancer versus control tissues. While our computational predictions were consistent with some of the previous observations, multiple novel predictions were made: (1) glutamine is generally not involved in

In aging and Alzheimers, the chemical signal glutamate can accumulate between neurons, damaging the circuitry, Pereira says. When we treated rats with riluzole, we saw a suite of changes. Perhaps most significantly, expression of molecules responsible for clearing excess glutamate returned to more youthful levels.. Previous work in McEwens lab by Pereira has shown that the drug prompted structural changes in rats neurons that prevent the memory loss often seen in old animals. Pereira is currently testing riluzole for the first time in Alzheimers patients in a clinical trial at the Rockefeller University Hospital. Glutamate clean up. Generally, glutamate is released to excite other neurons and doesnt linger in the spaces between them. As we age, though, the system gets a little leaky and glutamate can build up in these intercellular spaces. This happens in part when neurons make less and less of the transporter molecule responsible for removing excess glutamate. When it accumulates, this ...

TY - JOUR. T1 - A-fiber sensory input induces neuronal cell death in the dorsal horn of the adult rat spinal cord. AU - Coggeshall, Richard E.. AU - Lekan, Helena A.. AU - White, Fletcher A.. AU - Woolf, Clifford J.. PY - 2001/7/2. Y1 - 2001/7/2. N2 - Excitoxicity due to excessive synaptic glutamate release is featured in many neurological conditions in which neuronal death occurs. Whether activation of primary sensory pathways can ever produce sufficient over-activity in secondary sensory neurons in the dorsal horn of the spinal cord to induce cell death, however, has not been determined. In this study, we asked whether activity in myelinated afferents (A fibers), which use glutamate as a transmitter, can induce cell death in the dorsal horn. Using stereological estimates of neuron numbers from electron microscopic sections, we found that stimulation of A-fibers in an intact sciatic nerve at 10 Hz, 20 Hz, and 50 Hz in 10-minute intervals at a stimulus strength that activates both Aβ and Aδ ...

TY - JOUR. T1 - Excitotoxic injury to mitochondria isolated from cultured neurons. AU - Kushnareva, Yulia E.. AU - Wiley, Sandra E.. AU - Ward, Manus. AU - Andreyev, Alexander Y.. AU - Murphy, Anne N.. PY - 2005/8/12. Y1 - 2005/8/12. N2 - Neuronal death in response to excitotoxic levels of glutamate is dependent upon mitochondrial Ca 2+ accumulation and is associated with a drop in ATP levels and a loss in ionic homeostasis. Yet the mapping of temporal events in mitochondria subsequent to Ca 2+ sequestration is incomplete. By isolating mitochondria from primary cultures, we discovered that glutamate treatment of cortical neurons for 10 min caused 44% inhibition of ADP-stimulated respiration, whereas the maximal rate of electron transport (uncoupler-stimulated respiration) was inhibited by ∼10%. The Ca 2+ load in mitochondria from glutamate-treated neurons was estimated to be 167 ± 19 nmol/mg protein. The glutamate-induced Ca 2+ load was less than the maximal Ca 2+ uptake capacity of the ...

In the brain, termination of glutamatergic neurotransmission is achieved predominantly by rapid uptake of synaptically released glutamate into astrocytes through the sodium-dependent glutamate transporters GLT-1 and GLAST and its subsequent conversion to glutamine by the enzyme GS (Rothstein et al., 1996; Sonnewald et al., 1997). To date, several factors, including glutamate itself, have been identified that rapidly alter the activity of the glutamate uptake process by post-translational modification of glutamate transporters (for review, see Gegelashvili and Schousboe, 1998). However, the factor or factors regulating the expression of glial glutamate transporter as well as of GS are still unknown. Pronounced increases in glial expression levels of GLT-1, GLAST, and GS have been observed in coculture systems with neurons (Hayashi et al., 1988; Swanson et al., 1997; Schlag et al., 1998). Although originally it had been suggested that these effects involve glutamate signaling, recent work by ...

Under defined culture conditions, exogenous glutamate (Glu), NMDA, or an endogenous Glu-related toxin is lethal to rat retinal ganglion cells; these detrimental effects are NMDA receptor mediated because specific NMDA antagonists can prevent cellular injury. In the presence of an endogenous Glu-like toxin, 125 microM kainate (KA) increases the proportion of retinal ganglion cells that die, but the toxicity (due to both KA and the endogenous toxin) is totally prevented by 2-amino-5- phosphonovalerate (APV), a specific NMDA receptor antagonist. These findings indicate that the KA-induced portion of retinal ganglion cell death also appears to be mediated via NMDA receptors. There are at least 2 possible mechanisms for this lethal effect. In addition to KA receptors, KA could directly stimulate NMDA receptors. Alternatively, KA might activate its own specific receptor, which in turn leads to a net increase in the release of an endogenous Glu-related toxin; this endogenous substance would then ...

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The energetics of cerebral activity critically relies on the functional and metabolic interactions between neurons and astrocytes. Important open questions include the relation between neuronal versus astrocytic energy demand, glucose uptake and intercellular lactate transfer, as well as their dependence on the level of activity. We have developed a large-scale, constraint-based network model of the metabolic partnership between astrocytes and glutamatergic neurons that allows for a quantitative appraisal of the extent to which stoichiometry alone drives the energetics of the system. We find that the velocity of the glutamate-glutamine cycle (Vcyc) explains part of the uncoupling between glucose and oxygen utilization at increasing Vcyc levels. Thus, we are able to characterize different activation states in terms of the tissue oxygen-glucose index (OGI). Calculations show that glucose is taken up and metabolized according to cellular energy requirements, and that partitioning of the sugar between

TY - JOUR. T1 - Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. AU - Beppu, Kaoru. AU - Sasaki, Takuya. AU - Tanaka, Kenji. AU - Yamanaka, Akihiro. AU - Fukazawa, Yugo. AU - Shigemoto, Ryuichi. AU - Matsui, Ko. PY - 2014/1/22. Y1 - 2014/1/22. N2 - The brain demands high-energy supply and obstruction of blood flow causes rapid deterioration of the healthiness of brain cells. Two major events occur upon ischemia: acidosis and liberation of excess glutamate, which leads to excitotoxicity. However, cellular source of glutamate and its release mechanism upon ischemia remained unknown. Here we show a causal relationship between glial acidosis and neuronal excitotoxicity. As the major cation that flows through channelrhodopsin-2 (ChR2) is proton, this could be regarded as an optogenetic tool for instant intracellular acidification. Optical activation of ChR2 expressed in glial cells led to glial acidification and to release of glutamate. On the ...

ABSTRACT GLUTAMATE TRANSPORT AFFECTS MITOCHONDRIA AND CALCIUM SIGNALING IN ASTROCYTIC PROCESSES UNDER NORMAL AND PATHOLOGICAL CONDITIONS John Charles ODonnell Michael B. Robinson Mitochondria are responsible for synthesis and metabolism of the primary excitatory neurotransmitter, glutamate, which is cleared from synapses via Na+-dependent transporters on astrocytes. Astrocytic clearance of glutamate is required to prevent excitotoxic neuronal death. Mitochondria also participate in calcium signaling in various cell types. Astrocytic calcium signaling is implicated in neurovascular coupling. Glutamate transport and calcium signaling are central to the function of astrocytic processes that are in turn vital for normal brain function. We recently confirmed that mitochondria are present throughout astrocytic processes. Using confocal microscopy and hippocampal slice cultures along with a variety of biochemical assays, we sought to elucidate the physiological and pathological interactions between

System xc− represents an intriguing target in attempts to understand the pathological states of the central nervous system. Also called a cystine-glutamate antiporter, system xc− typically functions by exchanging one molecule of extracellular cystine for one molecule of intracellular glutamate. Nonvesicular glutamate released during cystine-glutamate exchange activates extrasynaptic glutamate receptors in a manner that shapes synaptic activity and plasticity. These findings contribute to the intriguing possibility that extracellular glutamate is regulated by a complex network of release and reuptake mechanisms, many of which are unique to glutamate and rarely depicted in models of excitatory signaling. Because system xc− is often expressed on non-neuronal cells, the study of cystine-glutamate exchange may advance the emerging viewpoint that glia are active contributors to information processing in the brain. It is noteworthy that system xc− is at the interface between excitatory signaling and

In this study, the pathophysiology of A−β+ KPD was investigated comprehensively using a two-step discovery method. First, fasting plasma metabolomics compared KPD patients to nondiabetic obese subjects. Hypotheses generated from key differences were tested by kinetic tracer studies targeting the suspected metabolic pathways in a fresh cohort of patients and control subjects.. The metabolomic analysis revealed signals of altered BCAA catabolism in KPD associated with changes in glutamine/glutamate. We hypothesized that the lack of elevated leucine in KPD was due to accelerated catabolism of this amino acid, indicated by decreased C5-AC and elevated glutamate (33,34). Evidence that accelerated leucine catabolism extended beyond isovaleryl CoA to β-methylcrotonyl CoA and ketogenesis was provided by the lower level of 3-hydroxyisovaleryl-carnitine (C5-OH). Concomitantly, glutamine was 50% lower, whereas glutamate was 175% higher, in KPD. Glutamine and glutamate are nitrogen sinks for catabolism ...

In this study, the pathophysiology of A−β+ KPD was investigated comprehensively using a two-step discovery method. First, fasting plasma metabolomics compared KPD patients to nondiabetic obese subjects. Hypotheses generated from key differences were tested by kinetic tracer studies targeting the suspected metabolic pathways in a fresh cohort of patients and control subjects.. The metabolomic analysis revealed signals of altered BCAA catabolism in KPD associated with changes in glutamine/glutamate. We hypothesized that the lack of elevated leucine in KPD was due to accelerated catabolism of this amino acid, indicated by decreased C5-AC and elevated glutamate (33,34). Evidence that accelerated leucine catabolism extended beyond isovaleryl CoA to β-methylcrotonyl CoA and ketogenesis was provided by the lower level of 3-hydroxyisovaleryl-carnitine (C5-OH). Concomitantly, glutamine was 50% lower, whereas glutamate was 175% higher, in KPD. Glutamine and glutamate are nitrogen sinks for catabolism ...

The mammalian genome contains four genes encoding GABA transporters (GAT1, slc6a1; GAT2, slc6a13; GAT3, slc6a11; BGT1, slc6a12) and five glutamate transporter genes (EAAT1, slc1a3; EAAT2, slc1a2; EAAT3, slc1a1; EAAT4, slc1a6; EAAT5, slc1a7). These transporters keep the extracellular levels of GABA and excitatory amino acids low and provide amino acids for metabolic purposes. The various transporters have different properties both with respect to their transport functions and with respect to their ability to act as ion channels. Further, they are differentially regulated. To understand the physiological roles of the individual transporter subtypes, it is necessary to obtain information on their distributions and expression levels. Quantitative data are important as the functional capacity is limited by the number of transporter molecules. The most important and most abundant transporters for removal of transmitter glutamate in the brain are EAAT2 (GLT-1) and EAAT1 (GLAST), while GAT1 and GAT3 are the

Lu Yihe, Y Timofeeva 2016 Response functions for electrically coupled neuronal network: a method of local point matching and its applications Biological Cybernetics, pp 1-17, doi: 10.1007/s00422-016-0681-y. Y Timofeeva, K Volynski 2015 Calmodulin as a major calcium buffer shaping vesicular release and short-term synaptic plasticity: facilitation through buffer dislocation Frontiers in Cellular Neuroscience 9:239, doi: 10.3389/fncel.2015.00239. Y S Ermolyuk, F G Alder, R Surges, I Y Pavlov, Y Timofeeva, D M Kullmann, K E Volynski 2013 Differential triggering of spontaneous glutamate release by P/Q-, N- and R-type Ca2+ channels, Nature Neuroscience, 16, 1754-1763, doi:10.1038/nn.3563. Y Timofeeva, S Coombes Network response of gap junction coupled dendrites, in Dendritic Computations through Morphology and Connectivity, Springer, 2013. Y Timofeeva Complexity and Chaos in Dynamical Systems, in Masters of Complexity Science, the London Mathematical Society Lecture Note Series, 2013. Y Timofeeva, ...

Is anyone taking ashwagandha? If so, what has been your experience with it? Has it had a noticeable effect on any MS symptoms? Water extract from the leaves of Withania somnifera protect RA differentiated C6 and IMR-32 cells against glutamate-induced ...

The aim of this study was to explore the modulation by α7 nicotinic receptors (nAChRs) of dopamine and glutamate release in the rat prefrontal cortex where these receptors are implicated in attentional processes and are therapeutic targets for cognitive deficits. The presence of presynaptic α7 nAChRs on glutamate terminals is supported by the ability of the subtype-selective agonist Compound A to evoke [3H]D-aspartate release from synaptosomes: This response was potentiated by the selective allosteric potentiator PNU-120596 and blocked by αbungarotoxin. Compound A also evoked dopamine overflow in the prefrontal cortex in vivo, and this was potentiated by PNU-120596. α7 nAChR-evoked [3H]dopamine release from tissue prisms in vitro was blocked by antagonists of NMDA and AMPA receptors. These data are consistent with a model in which α7 nAChRs present on glutamate terminals increase glutamate release that (1) contributes to presynaptic facilitation and synaptic plasticity and (2) co-ordinately ...

What is the difference between Glutamine and Glutamate? Glutamine is a conditionally essential amino acid while Glutamate is a non-essential amino acid. It is..

TY - JOUR. T1 - Re. T2 - Leptin signaling in GABA neurons, but not glutamate neurons, is required for reproductive function: Editorial comment. AU - Atala, Anthony. PY - 2014/1/1. Y1 - 2014/1/1. UR - http://www.scopus.com/inward/record.url?scp=84908173864&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=84908173864&partnerID=8YFLogxK. U2 - 10.1016/j.juro.2014.03.012. DO - 10.1016/j.juro.2014.03.012. M3 - Comment/debate. C2 - 25280328. AN - SCOPUS:84908173864. VL - 191. JO - Journal of Urology. JF - Journal of Urology. SN - 0022-5347. IS - 6. ER - ...

Summary is not available for the mouse gene. This summary is for the human ortholog.] L-glutamate is the major excitatory neurotransmitter in the central nervous system, and it activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors that have been divided into three groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5, and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3, while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Multiple transcript variants encoding different isoforms have been found for this gene. ...

Glutamate-induced delayed calcium dysregulation (DCD) is usually causally associated with excitotoxic neuronal death. Ro 25-6981, and Co 101244 inhibit NCXrev. The power of ifenprodil to inhibit NCXrev correlates using its effectiveness in avoiding DCD and stresses an important part of NCXrev in DCD. Overall our data claim that both NR2A- and NR2B-NMDARs get excited about DCD in old neurons, which is essential to inhibit both NMDARs and NCXrev to avoid glutamate-induced DCD. (Cull-Candy et al., 2001). Ifenprodil was discovered to become the 1st neuroprotective agent selective for NR2B-containing NMDARs (NR2B-NMDARs) (Carter et al., 1988; Carter et al., 1989; Williams, 1993). Significantly, ifenprodil escalates the strength of protons to stop the NMDAR (Mott et al., 1998) and protects neurons against glutamate excitotoxicity within an activity-dependent way (Kew et al., 1996). This system was suggested to significantly donate to ifenprodil effectiveness and having less negative effects of this ...

The activation of those Ca2+ waves can be induced, as it has been said before, by neurotransmitters which are released into the synaptic space surrounded by astrocytes terminations. Evidence of this mechanisms has been provided by research into the role of mGluR5 in astrocytes in the nucleus accumbens. This type of glutamate receptor has a major role in regulating Ca2+ signaling in astrocytes and, as a consequence, the Ca2+ dependent release of excitatory transmitters from these glia: activation of mGluR5 induces Ca2+ oscillations in NAcc astrocytes with the correlated appearance of NMDA receptor-dependent slow inward currents detected in nucleus accumbens neurons. In other words, glutamatergic afferents cause the sustained activation of astrocytes, which in turn excite the surrounding through extrasynaptic NMDA receptors: this might be involved in amplificating neuronal signals (mGluR5 stimulates gliotransmission in the nucleus accumbens, 2007).. The release of gliotransmitters can be mediated ...

The neurotransmitter glutamate has been implicated in multiple neurodegenerative studies. Researchers agree that glutamate excitotoxicity undoubtedly has a role in the pathogenesis of Alzheimer disease, the most common neurodegenerative pathology affecting the elderly population. Research suggests glutamate excitotoxicity accelerates the progression of Alzheimer disease.[12] Glutamate is also implicated in the pathogenesis of Parkinson disease. Mutations in genes encoding the parkin and DJ1 proteins are present in Parkinsons disease, which are involved in the regulation of excitatory glutamate synapses. These proteins may also protect neurons against glutamate excitotoxicity.[13][14]. Gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, is targeted in the treatment of anxiety disorder, insomnia, epilepsy, and other conditions. In particular, these drugs alter GABAergic function by targeting the GABAA and GABAB receptors.[15]. Not only does ...

The February 2007 issue of the American Journal of Neuroradiology reported the findings of A. Ciafoni et al.1 In this article, the authors reported the approach of examining glutamate/glutamine peaks in 1H-MR (proton) spectroscopy to increase the specificity in differentiating tumefactive demyelinating processes from neoplasms. The thought of using MR spectroscopy in this situation is attractive because the current clinical approach may warrant a lumbar puncture and even biopsy. Although we commend the authors enthusiasm for this technique, the paper lacks statistical significance and contains much bias to support the authors claim that MR spectroscopy can be helpful in the noninvasive diagnosis of acute demyelinating diseases1 when elevated glutamate/glutamine peaks are identified. We believe that this article should be represented as an idea backed by case reports and not be considered as original research.. First, the authors never fully give the inclusion or exclusion criteria for how ...

Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system.[21] At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the presynaptic cell. Glutamate acts on ionotropic and metabotropic (G-protein coupled) receptors.[21] In the opposing postsynaptic cell, glutamate receptors, such as the NMDA receptor or the AMPA receptor, bind glutamate and are activated. Because of its role in synaptic plasticity, glutamate is involved in cognitive functions such as learning and memory in the brain.[22] The form of plasticity known as long-term potentiation takes place at glutamatergic synapses in the hippocampus, neocortex, and other parts of the brain. Glutamate works not only as a point-to-point transmitter, but also through spill-over synaptic crosstalk between synapses in which summation of glutamate released from a neighboring synapse creates extrasynaptic signaling/volume transmission.[23] In addition, glutamate plays ...

It is known that nerve cells called motor neurons die in the brains and spinal cords of people with amyotrophic lateral sclerosis (ALS). However, the cause of this cell death is unknown. Researchers think that increased levels of a chemical called glutamate may be related to the cell death. For this reason researchers want to study drugs that decrease glutamate levels near nerves. Ceftriaxone-a semi-synthetic, third generation cephalosporin antibiotic-may increase the level of a protein that decreases glutamate levels near nerves. Studies of ceftriaxone in the laboratory suggest that it may protect motor neurons from injury.. Ceftriaxone is approved by the U.S. Food and Drug Administration (FDA) for treating bacterial infections but not for treating ALS. Also, ceftriaxone has not been given to people over a long period of time, such as months or years. The goals of this study are to evaluate the safety and effectiveness of ceftriaxone as a treatment for ALS, and to determine the safety and ...

l-glutamate (Glu) is the main excitatory neurotransmitter in the central nervous system (CNS) and is associated with motor behavior and sensory perception. While microdialysis methods have been used to record tonic levels of Glu, little is known about the more rapid changes in Glu signals that may be observed in awake rats. We have reported acute recording methods using enzyme-based microelectrode arrays (MEA) with fast response time and low detection levels of Glu in anesthetized animals with minimal interference. The current paper concerns modification of the MEA design to allow for reliable measures in the brain of conscious rats. In this study, we characterized the effects of chronic implantation of the MEA into the brains of rats. We were capable of measuring Glu levels for 7 days without loss of sensitivity. We performed studies of tail-pinch induced stress, which caused a robust biphasic increase in Glu. Histological data show chronic implantation of the MEAs caused minimal injury to the ...

Stroke is an acute brain health issue which causes neuronal damage which has currently no safe and effective neuroprotective treatment approaches. Immediately following a stroke, the brain tissue loses blood perfusion and the center of the infarct deteriorates quickly. This then causes milder ischemia and many brain cells or neurons will result in delayed death which can take up to several hours or even days. Research studies show that the mechanism of cell death is mainly NMDA receptor-dependent excitotoxicity. In ischemic areas, extracellular glutamate levels increase while preventing glutamate release, synaptic activity, or NMDAR activation which was capable of limiting cell death in a variety of stroke models. Thus, preventing excitotoxicity is an important treatment approach for reducing brain damage and improving patient outcome measures following a stroke, and this has definitely encouraged extensive efforts towards developing NMDA receptor-based stroke treatment approaches over the last ...

My laboratorys approach to understand brain is to reduce brain to various components and ultimately molecules. The primary functional component of brain is the neural circuit, which are comprised of anatomical neuronal wiring and synaptic transmission. Temporally, neurotransmission by a major excitatory neurotransmitter in brain, glutamate, is very quick and is clearly essential for brain function; however, the modulation of brain function underlying learning, memory, emotion, cognition, etc., happens on a different time scale than that of neurotransmission. Our broad goal is to understand how basic synaptic transmission can be modulated over seconds to hours, thereby supporting complex brain functions.The efficacy of synaptic transmission is determined by glutamate concentration at the synaptic cleft and by the number and channel properties of the glutamate receptors, which can be modulated by neuronal activation (synaptic plasticity).. It is therefore important to determine how many receptors ...

Significant advances have been made over recent years in our understanding of the tremendous complexity underlying the function of the human brain, in particular gaining insight into the mechanisms of synaptic plasticity which are key to developmental, adaptive and learning processes. Glutamate, the major excitatory neurotransmitter in the central nervous system (CNS), is of critical importance to these processes, acting at chemical synapses on two major classes of receptors - the metabotropic family of G-protein coupled receptors (mGluRs 1-8), and ionotropic family of ion channel forming receptors (iGluRs). The latter comprises the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA), N-methyl-d-aspartate (NMDA) and kainate receptors. Despite similarities shared within this ion channel family, there exist clear structural and pharmacological differences which underlie their individual modes of action. This chapter provides a case history of ion channel lead optimisation, discusses ...

Glutamate may be responsible for insomnia in patients with restless leg syndrome. Therefore, drugs reducing glutamate in the brain could be an answer to this insomnia.

Glutamate ((S)-Glu) is the major excitatory amino acid in the central nervous system. It acts by stimulating ionotropic and metabotropic glutamate receptors (iGluR and mGluR respectively). Glutamate has been shown to be involved not only in many neuropathologies such as anxiety, pain, ischemia, Parkinsons disease, epilepsy and schizophrenia. More recently, mGlu receptors have also been detected in non-neuronal cells suggesting that they could be implicated in carcinogenesis.. mGlu receptors are G-protein-coupled receptors and eight subtypes (mGluR1 to mGluR8) have been identified and classified into three groups (I-III) based upon sequence homology, transduction mechanism and pharmacological profile.. Because of their modulating properties, mGlu receptors are recognized as promising therapeutic targets and many ligands (agonists and antagonists) have been prepared to better understand the pharmacology of mGlu receptors in order to selectively activate the different groups and subtypes of ...

Focal symptoms and signs occurring during brain tumor clinical presentation are dependent on a number of factors. Location and rate of growth are the most critical, followed by overall lesion size and nature, whether infiltrating or causing the displacement of neural structures, but also the presence or extent of associated pathology, including edema, hemorrhage, vascular compromise, and cerebrospinal fluid obstruction. Mechanisms of presenting symptomatology can be divided into tumor and peritumoral factors. Tumor factors include histology, for example, in that seizures are common in patients with certain low-grade gliomas. Peritumoral factors, including regional hypoxia and ionic changes in the peritumoral zone, may influence neuronal activity and extracellular glutamate may be associated with neuronal hyperexcitability. Blood-brain barrier breakdown may predispose to seizure and localized neuronal dysfunction. Finally, signs and symptoms in brain tumors can be generalized, associated with increased

TY - JOUR. T1 - Tumour associated epilepsy and glutamate excitotoxicity in patients with gliomas. AU - Liubinas, Simon V.. AU - OBrien, Terence J.. AU - Moffat, Bradford M.. AU - Drummond, Katharine J.. AU - Morokoff, Andrew P.. AU - Kaye, Andrew H.. PY - 2014. Y1 - 2014. N2 - Tumour associated epilepsy (TAE) is common, debilitating and often not successfully controlled by surgical resection of the tumour and administration of multiple anti-epileptic drugs. It represents a cause of significant lost quality of life in an incurable disease and is therefore an important subject for ongoing research. The pathogenesis of TAE is likely to be multifactorial and involve, on the microscopic level, the interaction of genetic factors, changes in the peritumoural microenvironment, alterations in synaptic neurotransmitter release and re-uptake, and the excitotoxic effects of glutamate. On a macroscopic level, the occurrence of TAE is likely to be influenced by tumour size, location and interaction with ...

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Synaptic transmission of most vertebrate synapses is thought to be terminated by rapid transport of the neurotransmitter into presynaptic nerve terminals or neuroglia. L-Glutamate is the major excitatory transmitter in brain and its transport represents the mechanism by which it is removed from the …

Lindholm, D., Dechant, G., Heisenberg, C.-P. J., & Thoenen, H. (1993). Brain-derived neurotrophic factor is a survival factor for cultured rat cerebellar granule neurons and protects them against glutamate-induced neurotoxicity. European Journal of Neuroscience, 5(11), 1455-1464. https://doi.org/10.1111/j.1460-9568.1993.tb00213.x ...

Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium (PubMed:1374164). Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition; channels containing GRIN1 and GRIN2A have higher sensitivity to glutamate and faster kinetics than channels formed by GRIN1 and GRIN2B (By similarity). Contributes to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (PubMed:7816096, PubMed:8987814).

BioAssay record AID 676852 submitted by ChEMBL: Negative allosteric modulation of human mGluR5 expressed in HEK293A cells assessed as inhibition of glutamate-induced calcium flux by FLIPR method.