• Korean Journal of Biological Psychiatry
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• v.20 no.1
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• pp.1-5
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• 2013

Glutamate receptors are important components of synaptic transmission in the nervous system. Especially, ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors mediate most abundant excitatory synaptic transmission in the brain. There is elaborate mechanism of regulation of AMPA receptors including protein synthesis/degradation, intracellular trafficking, exocytosis/endocytosis and protein modification. In recent studies, it is revealed that functional dysregulation of AMPA receptors are related to major psychiatric disorders. In this review, we describe the structure and function of AMPA receptors in the synapse. We will introduce three steps of mechanism involving trafficking of AMPA receptors to neuronal membrane, lateral diffusion into synapses and synaptic retention by membrane proteins and postsynaptic scaffold proteins. Lastly, we will describe recent studies showing that regulation of AMPA receptors is important pathophysiological mechanism in psychiatric disorders.

• YAKHAK HOEJI
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• v.40 no.6
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• pp.720-726
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• 1996

The neurotoxicity induced by L-glutamate in primary cultures of rat cortical cells could be attenuated by diterpene constituents of Ginkgo biloba leaves, ginkgolides A, B and C. At the concentration of 100 nM, ginkgolides up-regulated the activity of glutathione reductase in primary cultures of rat cortical cells exposed to 100 ${\mu}$M glutamate. Furthermore, ginkgolides increased the content of reduced glutathione in glutamate-treated cortical cells. However, ginkgolides showed little effect in reducing superoxide dismutase activity. Ginkgolides did, however, markedly block the production of malondialdehyde, a byproduct of lipid peroxidation in glutamate-treated rat cortical cells.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.111-116
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• 1997

The neurotoxicity induced by L-glutamate in primary cultures of rat cortical cells could be attenuated by sesquiterpene constituent of Ginkgo biloba leaves, bilobalide. At the c oncentration of 100 nM, Bilobalide elevated the combined levels of reduced/oxidized glutathione in rat cortical cells exposed to 100 ${\mu}$M glutamate. Furthermore, bilobalide promoted a reduction in superoxide dismutase activity in glutamate-treated cells. Finally, bilobalide markedly inhibited the production of malondialdehyde. a measure of lipid peroxidation, in glutamate-treated rat cortical cells.

• Korean Journal of Pharmacognosy
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• v.50 no.2
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• pp.118-123
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• 2019

Glutamate acts as an important neurotransmitter in brain. However, high concentration of glutamate showed an excitatory neurotoxicity and resulted to neuronal cell death. Neuronal cell death is known for one of the reason of Alzheimer's disease, a neurodegenerative disease. We tried to find neuroprotective medicinal plants by neuroprotection activity against glutamate injured HT22 cells as a model system. In the course of bioscreening of various medicinal plants, Taraxacum platycarpum extract showed significant neuroprotective activity. We tried to elucidate mechanisms of neuroprotective activity. T. platycarpum extract reduced ROS and intracellular $Ca^{2+}$ concentration increased by glutamate induced neurotoxicity. In addition, mitochondrial membrane potential was restored to the control level. Also, glutathione level, glutathione reductase and glutathione peroxidase activity were increased by T. platycarpum extract treatment. These data suggested that T. platycarpum showed neuroprotective activity via antioxidative activity.

• Journal of Life Science
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• v.31 no.5
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• pp.520-526
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• 2021

Microbial protein is one of the sources of protein in the rumen and can also be the source of glutamate production. Glutamic acid is used as fuel in the metabolic reaction in the body and the synthesis of all proteins for muscle and other cell components, and it is essential for proper immune function. Moreover, it is used as a surfactant, buffer, chelating agent, flavor enhancer, and culture medium, as well as in agriculture for such things as growth supplements. Glutamic acid is a substrate in the bioproduction of gamma-aminobutyric acid (GABA). This review provides insights into the role of glutamic acid and glutamic acid-producing microorganisms that contain the glutamate decarboxylase gene. These glutamic acid-producing microorganisms could be used in producing GABA, which has been known to regulate body temperature, increase DM intake and milk production, and improve milk composition. Most of these glutamic acid and GABA-producing microorganisms are lactic acid-producing bacteria (LAB), such as the Lactococcus, Lactobacillus, Enterococcus, and Streptococcus species. Through GABA synthesis, succinate can be produced. With the help of succinate dehydrogenase, propionate, and other metabolites can be produced from succinate. Furthermore, clostridia, such as Clostridium tetanomorphum and anaerobic micrococci, ferment glutamate and form acetate and butyrate during fermentation. Propionate and other metabolites can provide energy through conversion to blood glucose in the liver that is needed for the mammary system to produce lactose and live weight gain. Hence, health status and growth rates in ruminants can be improved through the use of these glutamic acid and/or GABA-producing microorganisms.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.250-257
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• 2023

Glutamate is an excitatory neurotransmitter distributed in the central nervous system of mammals. However, high concentrations of glutamate are known to cause neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and stroke by causing nerve cell death. In this study, the antioxidant activity and neuroprotective effect of subtropical natural products were analyzed. Among 11 subtropical plant extracts mainly tested, Sallacca wallichiana extract (SE) showed the greatest free radical scavenging activity. Then, we confirmed through WST-1 assay that SE protected HT22 cells against glutamate-induced cell death in a concentration-dependent manner. The protective effects of SE against glutamate-induced apoptosis in HT22 cells were also confirmed by flow cytometry analysis using Annexin V/PI double staining. We also confirmed using H₂DCF-DA single staining that SE inhibits glutamate-induced intracellular reactive oxygen species. And we were confirmed through that SE inhibited glutamate-induced phosphorylation of Mitogen-activated Protein kinases. Consequently, our results propose that SE may contribute to the development of therapeutics to prevent neurodegenerative diseases.

• Korean Journal of Pharmacognosy
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• v.23 no.4
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• pp.259-263
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• 1992

The neuroprotective effect of betaine, one of the components of Lycii Fructus, on glutamate-induced neurotoxicity in primary cultured chicken brain cells were examined. Betaine was found to attenuate glutamate-induced neurotoxicity at the concentration of $5{\sim}10{\;}mM$ in both morphological and chemical aspects. The pretreatment of chicken brain cells with $5{\sim}10{\;}mM$betaine for 2hr at the 12 th day of culture before the 40min-exposure to $500\;{\mu}M$ glutamate significantly increased the survival rate of nerve cells in chicken brain. Betaine could also raise the decreased LDH-level in chicken brain cells which were induced neurotoxicity with $100\;{\mu}M$ glutamate. LDH value was decreased to 63% of control level in chicken brain cells at the time of 48 hr after the exposure to glutamate. However, the pretreatment of chicken brain cells with 5 mM betaine for 2 hr before the exposure to glutamate prevent the decrease of LDH in cells showing 90% of control level. Nevertheless, the remarkable neuroprotective effect of betaine on the glutamate-induced neurotoxicity in cultured chicken brain cells could not be observed when betaine was simultaneously administrated with glutamate.

• Korean Journal of Pharmacognosy
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• v.48 no.1
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• pp.31-37
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• 2017

Glutamate-induced oxidative stress results in neuro-degenerative disorders in many central nervous system (CNS) such as Alzheimer's disease, ischemia, Huntington's disease, and Parkinson's disease. Our study was performed to investigate neuroprotective effects of Allium hookeri extracts (leaf, root, and whole) on glutamate-induced HT22 cells. In this study, ethanol extract of A. hookeri showed the outstanding neuroprotective effect in HT22 cells. In addition, we found that ethanol extract of A. hookeri root increased heme oxygenase (HO)-1 in HT22 cells. Moreover, ethanol extract of A. hookeri root also upregulated nuclear accumulation of nuclear factor E2-related factor 2 (Nrf2) in HT22 cells. These results demonstrate that ethanol extract of A. hookeri root contributes neuroprotective effects against glutamate-induced oxidative stress in HT22 cells, via Nrf2-mediated HO-1 expression. Our study suggests that ethanol extract of A. hookeri root could be the potential agent for the treatment of many neuro-degenerative diseases.

• Korean Journal of Pharmacognosy
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• v.53 no.2
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• pp.79-86
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• 2022

Excessive glutamate causes oxidative stress in neuronal cells, which can cause degenerative neurological disorders. We tried to find medicinal plant showed neuroprotective activity by using glutamate-injured HT22 cell as a model system. In this study, we found that Boesenbergia rotunda methanol extract showed neuroprotective activity against glutamate induced neurotoxicity in mouse hippocampal HT22 cells. B. rotunda methanol extract suppressed the formation of reactive oxygen species and decreased intracellular Ca²⁺concentration. Also, B. rotunda made mitochondrial membrane potential maintain to normal levels. In addition, B. rotunda increased total glutathione amount and activated antioxidative enzyme such as glutathione reductase and glutathione peroxidase compared to glutamate-treated groups. These results suggested that B. rotunda decreased neuronal cell death damaged by high concentrations of glutamate treatment, via antioxidative mechanism and might be one of candidate of development of new drug to treat neurodegenerative disease such as Alzheimer's disease.

• Journal of Korean Ophthalmic Optics Society
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• v.18 no.4
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• pp.533-540
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• 2013

Purpose: To investigate the synaptic pattern of NMDA glutamate receptor subtype NMDA R1 on the dendritic arbors of ON-OFF direction-selective retinal ganglion cells (DS-RGSs) in developing [(5,10) days postnatal (PN)] mouse retina. Methods: ON-OFF DS-RGCs were injected with Lucifer yellow and the cells were identified by their characteristic morphology. To identify glutamatergic excitatory input from bipolar cell, we used a marker for the membrane traffic motor protein kinesin. Results: We identified DS-RGCs in P5, and P10 mouse retina. The immunofluorescence labeling of NMDA R1 was most prominent in the IPL. Our results showed that their presence upon the entire dendritic arbor of ON-OFF DS-RGCs is without any evidence of asymmetry, which would predict direction selectivity. Conclusions: The glutamatergic input from bipolar cell reveals symmetry pattern in all periods of P5, and P10. The results may suggest that direction selectivity not lies in the specific pattern of NMDA R1 receptors.