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Micronutrients for Improved Management of Huntington’s Disease
Published in Kedar N. Prasad, Micronutrients in Health and Disease, 2019
The levels of glutamate in the extracellular fluid are increased in HD brain. This could be due to a decrease in the glutamate transporter protein-1-dependednt uptake of glutamate. The two major glutamate transporter proteins, glutamate transporter-1 (GLT-1) and glutamate-aspartate transporter (GLAST) are primarily located in the astrocytes of adult brain and play an important role in maintaining physiological extracellular levels of glutamate. Release of ascorbate from the striatum into the extracellular fluid is reduced together with the reduction in GLT-1 dependent uptake of glutamate in mouse HD model (R6/2).98 Levels of ascorbate decrease and the levels of glutamate increase in the extracellular fluid of striatal neurons. The reduction in ascorbate levels and enhancement of glutamate would contribute to degeneration and death of the striatal neurons. Thus, reduction in the function of glutamate transporter proteins may contribute to degeneration of striatal neurons by decreasing the levels of vitamin C and increasing the levels of glutamate. Injection of vitamin C restored extracellular levels of vitamin C in R6/2 mice to the levels in wild-type mice and normalized neuronal function in the striatum of HD mice.98
Neurochemical pathology of dementia with Lewy bodies
Published in John O'Brien, Ian McKeith, David Ames, Edmond Chiu, Dementia with Lewy Bodies and Parkinson's Disease Dementia, 2005
Paul T Francis, Elaine K Perry, Margaret A Piggott, John E Duda
Only two studies have been published to date examining the glutamatergic system: they reported no change in the expression of a glutamate transporter protein in a small number of DLB cases (Scott et al, 2002) and reduced glutamate receptor immunoreactivity in the hippocampus and entorhinal cortex of patients with the Lewy body variant of AD (Thorns et al, 1997). Clearly, further studies are required to determine the possible role of glutamatergic neurons in DLB using a range of markers (Francis, 2003).
Atomic Force Microscopy of Biomembranes
Published in Qiu-Xing Jiang, New Techniques for Studying Biomembranes, 2020
Yi Ruan, Lorena Redondo-Morata, Simon Scheuring
Transporter proteins are key integral membrane proteins in many physiological processes. In the nervous system the glutamate transporter recovers the main excitatory neurotransmitter, glutamate, from the synaptic cleft. Their dysfunction is associated with many neurological diseases, such as epilepsy, Alzheimer’s disease, and amyotrophic lateral sclerosis. The glutamate transporter crystal structures of a prokaryotic homolog of archaebacterium Pyrococcus horikoshii is solved in both the outward- and inward-facing conformations of the sodium/aspartate symporter termed GltPh to reveal the molecular basis of the transport mechanism.64 HS-AFM imaging revealed directly the “elevator” typ transport mechanism of GltPh, where each transporter domain moves vertically across the membrane, as shown in Figure 5.11. HS-AFM also revealed non-cooperativity between the subunits in the trimeric GltPh. In order to show how the environmental conditions, the ligand, co-factor or inhibitor TBOA (DL-threo-β-Benzyloxyaspartic acid) concentrations, change GltPh activity and its transport dynamics. Real-time buffer transition experiments are performed using HS-AFM coupled to a buffer-exchange system. By exchanging the measuring buffer (using blue, red tubes in Figure 5.5) from a substrate-free condition to a NaCl/aspartate-rich environment, or by the injection of the inhibitor TBOA, it was shown that there is a rather gradual silencing of GltPh activity upon the addition of Na+ with an approximate half-maximal activity in the presence of NaCl at a few hundred mM. In case of TBOA addition, the vast majority of transporters are quiescent at ~100 µM TBOA.27
A mechanistic overview of spinal cord injury, oxidative DNA damage repair and neuroprotective therapies
Published in International Journal of Neuroscience, 2023
Jaspreet Kaur, Aditya Mojumdar
A pathological condition occurs by over-activation of glutamatergic receptors leading to neuronal cell death, the mechanism is known as excitotoxicity [38, 42–44]. At the normal synapse level, the glutamate excitation is efficiently terminated by glutamate uptake mechanisms of nerve and glial cells [45]. There are specific transporter proteins in the cells that uptake the glutamate by using the electrochemical potential gradient of Na+ and K+ ions. It is an efficient mechanism of maintaining a higher intracellular glutamate concentration compared to the extracellular level. Several glutamate transporter proteins, excitatory amino acid transporters 1 to 5, have been studied and reviewed [46,47]. The mainly studied excitatory amino acid receptors are – N-methyl-D-aspartate (NMDA) receptors, α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainate receptors. In physiologic conditions, these ion channels facilitate glutamate-mediated synaptic transmission. They have been studied and reviewed in detail [48–51].
Change in gene expression levels of GABA, glutamate and neurosteroid pathways due to acoustic trauma in the cochlea
Published in Journal of Neurogenetics, 2021
Meltem Cerrah Gunes, Murat Salih Gunes, Alperen Vural, Fatma Aybuga, Arslan Bayram, Keziban Korkmaz Bayram, Mehmet Ilhan Sahin, Muhammet Ensar Dogan, Sevda Yesim Ozdemir, Yusuf Ozkul
Glutamate released by inner hair cells into the synaptic cleft is taken by dendrites of afferent spiral ganglion neurons (SGNs) via N-methyl-D-aspartate (NMDA) and non-NMDA receptors (Ruel, Chen, Pujol, Bobbin, & Puel, 1999). Increased glutamate in the synaptic cleft induces intracellular Ca2+ entry and triggers a cascade of metabolic events leading to activation of enzymes such as phospholipases, proteases, endonucleases, which can cause cell death in SGNs (Steinbach & Lutz, 2007). Improvement in some symptoms after the use of NMDA receptor antagonists in the treatment of AT supports that noise causes changes in NMDA receptor subunit expression (Guitton & Dudai, 2007; Ohinata, Miller, & Schacht, 2003). Some deficiencies of glutamate uptake systems which remove glutamate from the extracellular space such as glutamate transporter (GLAST/EAAT1) deficiency have also been reported after AT (Hakuba, Koga, Gyo, Usami, & Tanaka, 2000).
Glutamatergic dysregulation in mood disorders: opportunities for the discovery of novel drug targets
Published in Expert Opinion on Therapeutic Targets, 2020
Panek Małgorzata, Kawalec Paweł, Malinowska Lipień Iwona, Tomasz Brzostek, Pilc Andrzej
Glutamate is the main stimulatory neurotransmitter in the central nervous system. Glu is the anion of glutamic acid and is the predominant form in physiological conditions. It plays an important role in the maturation of neurons, regulating their proliferation and migration processes during nervous system development. Additionally, it has a significant impact on cognition (e.g. learning and memory) as well as many other processes (e.g. it regulates the conduction of pain sensation in the spinal cord and brain). Glu is synthesized from glutamine in glutamatergic neurons by the mitochondrial enzyme glutaminase. With the aid of the vesicular glutamate transporter, Glu enters synaptic vesicles. During neuronal depolarization, the released Glu enters the synaptic space, stimulating numerous receptors. After its release, glutamate does not undergo enzymatic decomposition but is intercepted into the neighboring glial cells through the EAAT. Then, under the influence of the glutamine synthetase enzyme, it is converted into glutamine [13,25] Centelles et al. [25] depicted graphically the exact metabolism of glutamate)