• 대한한의학회지
• /
• 제21권1호
• /
• pp.11-19
• /
• 2000

The present study was carried out to investigate the effects of Woowhangcheongshim-won(WCW) on the extracellular concentrations of amino acid neurotransmitters(glutamate, aspartate, GABA, glycine, taurine, alanine, and tyrosine) and organic acid (lactate and pyruvate) in striatum and cerebral infarction volume in rats subjected to permanent focal cerebral ischemia induced by 2 hours of middle cerebral artery occlusion(MCAO), using intracerebral microdialysis as the sampling technique, Microdialysis probes were inserted into the lateral part of the caudate-putamen 2 hours before the experiment and microdialyzates were collected at 20min intervals and analyzed by high performance liquid chromatography, WCW significantly decreased the infarction volume with reducing focal cerebral ischemia-induced increase of extracellular glutamate, asparate, and tyrosine. On the other hand, the increase of GABA and taurine was enhanced after treatment of WCW in the ischemia-induced rats, These results suggest that WCW can produce a neuroprotective effect against cerebral ischemia by regulating extracellular excitatory and inhibitory amino acid levels in relation to the concept of excitotoxicity in brain ischemia.

• Restorative Dentistry and Endodontics
• /
• 제20권2호
• /
• pp.423-431
• /
• 1995

Trigeminal spinal sensory nucleus is a main relay site in transmission of orofacial pain. Glutamate and aspartate playa role in transmission of primary afferents. This experiment was performed to study the role of capsaicin, KR-25018 and shogaol on the release of glutamate and aspartate from trigeminal spinal sensory nucleus. Release of excitatory amino acids(EAAs) was induced by electrical stimulation of oral mucosa with innocuous or noxious stimuli. Capsaicin($10{\mu}M$), KR-25018($10{\mu}M$), shogaol($10{\mu}M$), ruthenium red and capsazapine were added to perfusion solution to observe the changes in EAA release, and glutamate and aspartate were determined by HPLC. Release of glutamate and aspartate from trigeminal sensory nucleus was increased by noxious stimulation of oral mucosa, but innocuous stimulation did not affect on the release of EAA Capsaicin and KR-25018 increased the release of glutamate and aspartate, and effect of KR-25018 on release of EAA was more potent than capsaicin. But shogaol had a weak effect on release of EAA. Effect of capsaicin and KR-25018 was partially blocked by capsaicin antagonists, ruthenium red and capsazepine.

• The Korean Journal of Physiology and Pharmacology
• /
• 제1권6호
• /
• pp.699-705
• /
• 1997

Although it is known that neuronal cell death during development occurs by apoptosis, the mechanisms underlying excitatory amino acid-induced neuronal cell death remain poorly understood. In this study we have examined the mechanism by which L-glutamate, an excitatory amino acid neurotransmitter, induces cell death in PC12 cell lines. To characterize cell death, we employed sandwich enzyme-linked immunosorbent assay(ELISA) method for cellular DNA fragmentation, DNA agarose gel electrophoresis and chromatin staining by acridine orange and ethidium bromide after treating the PC12 cells with L-glutamate. L-Glutamate caused dose-dependent cell death with a maximum at 24 hrs after the treatment. These cellular fragmentation was blocked by pretreatment of MK-801, a noncompetitive N-methyl-D-aspartic acid(NMDA) receptor antagonist, and nerve growth factor(NGF). Analysis of DNA integrity from L-glutamate-treated cells revealed cleavage of DNA into regular sized fragments, a biochemical hallmark of apoptosis. The PC12 cells that were induced to die by L-glutamate treatment exhibited classical chromatin condensation under the light microscopy after acridine orange and ethidium bromide staining. These results suggest that apoptosis is one of the key features that are involved in L-glutamate-induced excitotoxic cell death in PC12 cells, and these cell death are mediated by NMDA receptor and depend on NGF.

• 한국응용약물학회:학술대회논문집
• /
• 한국응용약물학회 1996년도 춘계학술대회
• /
• pp.211-211
• /
• 1996

Changes in glutamate release and uptake on cerebellar cells after the chronic exposure to lead were investigated. Rats were received 0.25% lead acetate in drinking water from the beginning of the pregnancy. The control group was given 0.125% sodium acetate in drinking water. The cerebellar cells from 7 or 8 day-old pups were cultured. Amino acid release from cerebellar granule cells and the glutamate uptake into cerebellar glial cells were measured using HPLC-ECD. Basal glutamate release and NMDA-induced glutamate release didn't show significant difference. However, the other amino acids in the granule cells obtained from lead exposed pups were less released than the control after the stimulation by NMDA (50$\mu$M). SNAP-induced (50$\mu$M) glutamate release was significantly reduced in granule cells prepared from lead exposed pups. The basal glutamate uptake in glial cells didn't show any difference. However, the uptake in glial cells prepared from lead exposed pups was significantly less blocked by PDC (24$\mu$M) compared to the control group. These results indicate that lead exposure to the mother might affect the Excitatory amino acid system during the development of the offspring.

• 대한한방내과학회지
• /
• 제21권1호
• /
• pp.116-125
• /
• 2000

Objectives : The aim of this study is to investigate that Sunghyangjeongki-San which has been frequently medicated in the early stage of stroke can protect against ischemic damage in rat brain Methods : Extracellular levels of amino acids(glutamate, aspartate, GABA, glycine, taurine, tyrosine, alanine), organic acids(pyruvate, lactate), and cerebral infarction volume were measured at the striatum of rats subjected to permanant focal cerebral ischemia induced by 2 hours of middle cerebral artery occiusion(MCAO). Rats were orally administered with Sunghyangjeongki-San at 30mins before MCAO and the microdialysate was collected by intracerebral microdialysis three times before MCAO and six times after MCAO at 20mins interval and analyzed by HPLC. After a microdialysis study, the brain was sliced and stained with cresyl violet buffer for the measurement of cerebral infarcted area and volume by image analyzer system Results : The concentrations of glutamate, aspartate, and tyrosine known as excitatory neurotransmitters were significantly decreased in Sunghyangjeongki-San group compared with control group, The concentrations of GABA, glycine, taurine and alanine known as inhibitory neurotransmitters were significantly increased in Sunghyangjeongki-San group compared with control group. The concentrations of pyruvate and lactate showed little significant change in Sunghyangjeongki-San group compared with control group. The measurement of cerebral infarcted area and volume by image analyzer system were significantly decreased in Sunghyangjeongki-San group compared with control group. Conclusions : Sunghyangjeongki-San can affect on protecting against cerebral ischemia by regulating extracellular levels of excitatory and inhibitory amino acid neurotransmitters and improve the conditions of the patients in the early stage of stroke.

• BMB Reports
• /
• 제39권3호
• /
• pp.284-291
• /
• 2006

In this study, the cDNA of a new peptide from the venom of the scorpion, Buthotus saulcyi, was cloned and sequenced. It codes for a 64 residues peptide (Bsaul1) which shares high sequence similarity with depressant insect toxins of scorpions. The differences between them mainly appear in the loop1 which connects the $\beta$-strand1 to the $\alpha$-helix and seems to be functionally important in long chain scorpion neurotoxins. This loop is three amino acids longer in Bsaul1 compared to other depressant toxins. A comparative amino acid sequence analysis done on Bsaul1 and some of $\alpha$-, $\beta$-, excitatory and depressant toxins of scorpions showed that Bsaul1 contains all the residues which are highly conserved among long chain scorpion neurotoxins. Structural model of Bsaul1 was generated using Ts1 (a $\beta$-toxin that competes with the depressant insect toxins for binding to $Na^+$ channels) as template. According to the molecular model of Bsaul1, the folding of the polypeptide chain is being composed of an anti-parallel three-stranded $\beta$-sheet and a stretch of $\alpha$-helix, tightly bound by a set of four disulfide bridges. A striking similarity in the spatial arrangement of some critical residues was shown by superposition of the backbone conformation of Bsaul1 and Ts1.

• 한국버섯학회지
• /
• 제17권4호
• /
• pp.275-283
• /
• 2019

Sparassis latifolia is a fungus abundant in β-glucan and amino acids and is highly valued as a medicinal mushroom. Among amino acids, γ-aminobutyric acid (GABA) is a free amino acid and has biological effects, such as increase/decrease of hypertension, improvement of cerebral blood flow, and prevention of dementia. In this study, biological elicitors were used to increase bioactive substances as a biofortification method. Sodium alginate extracted from seaweed (Sargassum horneri, Sargassum fulvellum, Sargassum fusiforme) were used as the elicitor. The levels of β-glucan and GABA in the mycelium and fruiting body grown by adding the elicitor to the medium were investigated. Addition of sodium alginate positively affected GABA production and negatively affected the β-glucan production in these fungi. Sodium alginates extracted from S. fulvellum induced the highest increase in GABA in the mycelium and fruiting bodies. Moreover, we investigated the effects of the extracts from mycelium and fruiting bodies on dendrite development in primary cortical neurons. We found that the extract from the fruiting bodies of sodium alginate treated fungi with increased levels of GABA inhibited the dendrite outgrowth of excitatory neurons, but not inhibitory neurons.

• 수면정신생리
• /
• 제7권1호
• /
• pp.10-17
• /
• 2000

To investigate the neurobiological bases of learning and memory is one of the ambitious goals of modern neuroscience. The progress in this field of recent years has not only brought us closer to understanding the molecular mechanism underlying long-lasting changes in synaptic strength, but it has also provided further evidence that these mechanisms are required for memory formation. Since twenty years ago, several studies for the tests of the hypothesis that NMDA-dependent hippocampal long-term potentiation(LTP) underlies learning have been reported. Also, in the recent year, data from mutant mice showed that a potential role for NMDA-dependent LTP in hippocampal CA1 and spatial learning. Although the current evidence for the role of NMDA receptor in learning and memory is not still obvious, NMDA receptor seems to act as a critical switch for activation of a cascade of events that underlie synaptic plasticity.

• 생물정신의학
• /
• 제20권1호
• /
• pp.1-5
• /
• 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.

• 대한수의학회지
• /
• 제38권3호
• /
• pp.535-543
• /
• 1998

In the present study, we designed and constructed new microdialysis probe in order to improve the efficacy and accuracy of microdialysis method. In addition, extracellular concentrations of GABA, glutamate, aspartate and glycine were monitored with new designed probe in the lateral portion of the ventrocaudal periaqueductal gray using unanesthetized and unrestrained rats. Furthermore, the effect of opiates on release of these amino acids, especially GABA, was analyzed by measuring their concentration in PAG dialysates following veratridine administration in the presence of systemic morphine. The results were summerized as follow : 1. The damaging rates of 1.0mm or 1.5mm window probe were 12.5% or 42.8%, respectively. In the group using 1.5mm window probe, the damaging area was extended into mesencephalic aqueduct because of microdialyzing pressure. 2. Because of the unique design of our probes with an opening facing one side, dialysis occurs in a hemisphere($600{\mu}m$ in mediolateral direction and $100{\mu}m$ in opposite side of the dialysis probe) around the opening rather than in a spherical shaped configuration which is typical of most commercially available probe designs. 3. Glutamate, taurine and glycine were present in the highest concentration in the dialysate sample obtained before treatment with veratridine, whereas, aspartate and GABA were present in the lowest concentration. 4. The concentration of all 5 amino acids increased significantly following $75{\mu}m$ veratridine perfusion into lateral ventrocaudal PAG. 5. There was no significant difference between basal and peak amino acid concentrations according to window sizes. 6. Morphine had no effect on baseline concentrations of amino acids in dialysates obtained from the lateral PAG as compared to saline treated controls. However, following veratridine treatment, morphine selectively affected GABA release in the lateral ventrocaudal PAG as compared to saline treated controls. These results suggest that GABAergic interneurons in the PAG are inhibited by opioids. Therefore, endogenous enkephalins or endorphins may directly inhibit intrinsic GABAergic intemeurons and block their tonic inhibition of PAG-NMR projection neurons. Moreover, new designed probes demonstrate improved efficiency and accuracy in collecting samples as compared to commercial types of microdialysis probes.