• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.728-737
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• 2003

This study was investigated to prove the effect of GMGHT on the gultamate receptor, free radical and brain damage in rats sujected to Brain Ischemia The results were as follows; 1, GMGHT showed significant inhibitory effect of GMGHT on LDH release induced by NMDA, AMPA, and kinate. 2. GMGHT showed significant inhibitory effect of GMGHT on LDH release induced by BSO and Fe/sup 2+/. 3. GMGHT decreased coma duration time in a infatal dose of KCN and showed 30% of survival rate in a fatal dose. 4. GMGHT decreased ischemic area and edema incited by the MCA blood flow block. 5. GMGHT showed improvement of forelimb and hindlimb test after MCA occulusion in neurological exemination. 6. GMGHT showed no significant change after MCA occulusion in pathological observation as normal group. These results indicate that GMGHT can be used in the brain damage sujected to Brain Ischemia. Further study will be needed about the functional mechanism and etc.

• Clinical and Experimental Reproductive Medicine
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• v.47 no.3
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• pp.207-212
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• 2020

Objective: Glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) is a subunit of a ligand-gated ion channel that regulates the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by controlling the release of gonadotropin-releasing hormone. Few studies have investigated the association between the GRIA1 gene and human infertility. This study evaluated the association of the GRIA1 rs548294 C > T and rs2195450 G > A polymorphisms with the ovarian response to human menopausal gonadotropin (HMG) in Iranian women. Methods: One hundred women with histories of at least 1 year of infertility were included. On the second day of menstruation, patients were injected with HMG; on the third day, blood samples were collected. After hormonal analysis, the GRIA1 rs548294 C > T and rs2195450 G > A genotypes of samples were identified via the restriction fragment length polymorphism method, and on day 9, the number of follicles was assessed via ultrasound. Results: For the GRIA1 rs548294 C > T and rs2195450 G > A single nucleotide polymorphisms, the subjects with CT and GG genotypes, respectively, displayed the highest mean FSH level, LH level, and number of follicles on day 9 of the menstrual cycle (p< 0.05). Significant positive correlations were observed between LH and FSH (p< 0.01), LH and follicle count (p< 0.01), FSH and age (p< 0.05), follicle count and age (p= 0.048), and FSH and follicle count (p< 0.01). Conclusion: This study showed a significant relationship between GRIA1 polymorphisms and ovarian response to the induction of ovulation. Therefore, determining patients' GRIA1 genotype may be useful for improving treatment and prescribing suitable doses of ovulation-stimulating drugs.

• Biomedical Science Letters
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• v.11 no.3
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• pp.319-326
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• 2005

It is well known that oxidative stress of reactive oxygen species (ROS) may be a causative factor in the pathenogenesis of bone disorder on osteoblast or osteoclast. The purpose of this study was to evaluate the cytotoxicity of oxidative stress, protective effect of glutamate receptor antagoinst against ROS-induced osteotoxicity, secretion of tumor necrosis factor $(TNF)-\alpha$ and the expression of c-fos gene in the cultured rat osteoblasts and osteoclasts. Cell viability by MTS assay or !NT assay, activity of glutathione peroxidase (GPx), lipid peroxidation (LPO) activity, protein synthesis by sulforhodamine B (SRB) assay, alkaline phosphatase (ALP) activity, lactate dehydrogenase (LDH) activity, MTS assay for NMDA (N-methyl-D-aspartate) receptor antagonist or AMPA/kainate receptor antagonist, measurement for $TNF-\alpha$, and c-fos gene expression were performed after these cells were treated with or without various cocentrations of xanthine oxidase (XO), hypoxanthine (HX), D-2-amino-5-phosphonovaleric acid (APV), 7-chlorokynurenic acid (CKA), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX), respectively. In this study, XO/HX showed decreased cell viability and glutathione peroxidase (GPx) activity, but it showed increased LPO activity, $TNF-\alpha$ secretion and c-fos expression. APV and CKA incresed protein sythesis and ALP activity. While, CNQX or DNQX did not show any protective effect in LDH activity or cell viability. From these results, XO/HX showed cytotoxic effect in cultured rat osteoblast or osteoclast, and also NMDA receptor antagonist such as APV or CKA was effective in blocking XO/HX-induced osteotoxicity in these cultures.

• International Journal of Oral Biology
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• v.34 no.2
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• pp.97-103
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• 2009

L-trans-pyrrolidine-2,4-dicarboxylate (PDC) is a potent inhibitor of glutamate transporters. In our current study, we investigated whether the neuronal death induced by PDC involves mechanisms other than excitotoxicity in mixed mouse cortical cultures. Cortical cultures at 13-14 days in vitro were used and cell death was assessed by measuring the lactate dehydrogenase efflux into bathing media. Glutamate and PDC both induced neuronal death in a concentration-dependent manner but the neurotoxic effects of glutamate were found to be more potent than those of PDC. Treatment with 10, 100 and 200 ${\mu}$M PDC equally potentiated 50 ${\mu}$M glutamate-induced neuronal death. The neuronal death induced by 75 ${\mu}$M glutamate was almost abolished by treatment with the NMDA antagonists, MK-801 and AP-5, but was unaffected by NBQX (an AMPA antagonist), trolox (antioxidant), BDNF or ZVAD-FMK (a pan-caspase inhibitor). However, the neuronal death induced by 200 ${\mu}$M PDC was partially but significantly attenuated by single treatments with MK-801, AP-5, trolox, BDNF or ZVAD-FMK but not NBQX. Combined treatments with MK-801 plus trolox, MK-801 plus ZVAD-FMK or MK-801 plus BDNF almost abolished neuronal death, whereas combined treatments with trolox plus ZVADFMK, trolox plus BDNF or ZVAD-FMK plus BDNF did not enhance the inhibitory action of any single treatment with these drugs. These results demonstrate that the neuronal death induced by PDC involves not only in the excitotoxicity induced by the accumulation of glutamate but also the oxidative stress induced by free radical generation. This suggests that apoptotic neuronal death plays a role in PDCinduced oxidative neuronal injury.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.265-273
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• 2004

KBPTS is the fortified prescription of Bang-pung-tong-sung-san (BPTS) by adding Spatholobi Clulis and Salviae Miltiorrzae Radix. BPTS prescription has been used in Qriental medicine for the treatments of vascular diseases including hypertension, stroke, and arteriosclerosis, and nervous system diseases. Yet, the overall mechanism underlying its activity at the cellular levels remains unknown. To investigate the protective role of KBPTS on brain functions, noxious stimulations were applied to neurons in vitro and in vivo. KBPTS pretreatment in cultured cortical neurons of albino ICR mice rescued death caused by AMPA, NMDA, and kainate as well as by buthionine sulfoximine (BSO) and ferrous chloride (Fe/sup 2+/) treatments. Furthermore, KBPTS promoted animal's recovery from coma induced by a sublethal dose of KCN and improved survival by a lethal dose of KCN. To examine its physiological effects on the nervous system, we induced ischemia in the Sprague-Dawley rat's brain by middle cerebral artery (MCA) occlusion. Neurological examination showed that KBPTS reduced the time which is required for the animal after MCA occlusion to respond in terms of forelimb and hindlimb movement$. Histological examination revealed that KBPTS reduced ischemic area and edema rate and also protected neurons in the cerebral cortex and hippocampus from ischemic damage. Thus, the present data suggest that KBPTS may play an important role in protecting neuronal cells from external noxious stimulations.

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.1-18
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• 2012

Schizophrenia is a devastating psychiatric illness that afflicts 1% of the population worldwide, resulting in substantial impact to patients, their families, and health care delivery systems. For many years, schizophrenia has been felt to be associated with dysregulated dopaminergic neurotransmission as a key feature of the pathophysiology of the illness. Although numerous studies point to dopaminergic abnormalities in schizophrenia, dopamine dysfunction cannot completely account for all of the symptoms seen in schizophrenia, and dopamine-based treatments are often inadequate and can be associated with serious side effects. More recently, converging lines of evidence have suggested that there are abnormalities of glutamate transmission in schizophrenia. Glutamatergic neurotransmission involves numerous molecules that facilitate glutamate release, receptor activation, glutamate reuptake, and other synaptic activities. Evidence for glutamatergic abnormalities in schizophrenia primarily has implicated the NMDA and AMPA subtypes of the glutamate receptor. The expression of these receptors and other molecules associated with glutamate neurotransmission has been systematically studied in the brain in schizophrenia. These studies have generally revealed region- and molecule-specifi c changes in glutamate receptor transcript and protein expression in this illness. Given that glutamatergic neurotransmission has been implicated in the pathophysiology of schizophrenia, recent drug development efforts have targeted the glutamate system. Much effort to date has focused on modulation of the NMDA receptor, although more recently other glutamate receptors and transporters have been the targets of drug development. These efforts have been promising thus far, and ongoing efforts to develop additional drugs that modulate glutamatergic neurotransmission are underway that may hold the potential for novel classes of more effective treatments for this serious psychiatric illness.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.33-45
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• 2008

Auditory fear memory is thought to be maintained by fear conditioning-induced potentiation of synaptic efficacy. The conditioning-induced potentiation has been shown to be maintained, at least in part, by enhanced expression of surface AMPA receptor (AMPAR) at excitatory synapses in the lateral amygdala (LA). Depotentiation, reversal of conditioning-induced potentiation, has been proposed as a cellular mechanism for fear extinction. However, a direct link between depotentiation and extinction has not yet been tested. To address this, we applied both ex vivo and in vivo approaches to rats in which fear memory had been consolidated. We found a novel form of ex vivo depotentiation; the depotentiation reversed conditioning-induced potentiation at thalamic input synapses onto the LA (T-LA synapses) ex vivo, and it could be induced only when both NMDA and metabotropic glutamate receptors were co-activated. Extinction returned the enhanced T-LA synaptic efficacy observed in conditioned rats to baseline and occluded the depotentiation. Consistently, extinction reversed conditioning-induced enhancement of surface expression of AMPAR subunits in LA synaptosomal preparations. A GluR2-derived peptide that blocks regulated AMPAR endocytosis inhibited depotentiation, and microinjection of a cell-permeable form of the peptide into the LA attenuated extinction. Our results are consistent with the use of depotentiation to weaken potentiated synaptic inputs onto the LA during extinction, and they provide strong evidence that AMPAR removal at excitatory synapses in the LA underlies extinction. The results described here are in line with previous findings. Neural activity in the LA has been shown to decrease after extinction in the rat and human. The NMDAR dependency of the depotentiation fits nicely with a large body of evidence that fear extinction depends upon amygdala NMDARs. Similarly, blockade of metabotropic glutamate recepotrs in the LA has recently been shown to attenuate fear extinction.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.72-83
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• 2003

Objective : The goal of the present study was to investigate the protective effect of Gamiheechum-tang (Jiaweixiqian-tang; GHCT) on brain tissue damage from chemical or ischemic insults. Methods : Levels of cultured cortical neuron death caused by toxic chemicals were measured by LDH release assay. Neuroprotective effects of GHCT on brain tissues were examined in vivo by ischemic model of middle cerebral artery (MCA) occlusion. Results : Animal groups treated with GBCT showed significantly decreased hypertension, and reduced levels of aldosterone, dopamine, and epinephrine in the plasma. GHCT treatments ($l0-200\mu\textrm{g}/ml$) significantly decreased cultured cortical neuron death mediated by AMPA, kainate, BSO, or Fe2+ when measured by LDH release assay. Yet, cell death mediated by NMDA was effectively protected by GHCT at the highest concentration examined ($200\mu\textrm{g}/ml$). In the in vivo experiment examining brain damage by MCA occlusion, affected brain areas by ischemic damage and edema were significantly less in animal groups administered with GHCT compared to the non-treated control group. Neurological examinations of forelimbs and hindlimbs showed that GHCT treatment improved animals' recovery from ischemic injury. Moreover, the extent of injury in cortical and hippocampal pyramidal neurons in ischemic rats was much reduced by GHCT, whose morphological features were similarly observed in non-ischemic animals. Conclusion : The present data suggest that GBCT may play an important role in protecting brain tissues from chemical or ischemic injuries.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.675-686
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• 2017

Orthostatic hypotension (OH) is associated with symptoms including headache, dizziness, and syncope. The incidence of OH increases with age. Attenuation of the vestibulosympathetic reflex (VSR) is also associated with an increased incidence of OH. In order to understand the pathophysiology of OH, we investigated the physiological characteristics of the VSR in the disorder. We applied sodium nitroprusside (SNP) to conscious rats with sinoaortic denervation in order to induce hypotension. Expression of pERK in the intermediolateral cell column (IMC) of the T4~7 thoracic spinal regions, blood epinephrine levels, and blood pressure were evaluated following the administration of glutamate and/or SNP. SNP-induced hypotension led to increased pERK expression in the medial vestibular nucleus (MVN), rostral ventrolateral medullary nucleus (RVLM) and the IMC, as well as increased blood epinephrine levels. We co-administered either a glutamate receptor agonist or a glutamate receptor antagonist to the MVN or the RVLM. The administration of the glutamate receptor agonists, AMPA or NMDA, to the MVN or RVLM led to elevated blood pressure, increased pERK expression in the IMC, and increased blood epinephrine levels. Administration of the glutamate receptor antagonists, CNQX or MK801, to the MVN or RVLM attenuated the increased pERK expression and blood epinephrine levels caused by SNP-induced hypotension. These results suggest that two components of the pathway which maintains blood pressure are involved in the VSR induced by SNP. These are the neurogenic control of blood pressure via the RVLM and the humoral control of blood pressure via epinephrine release from the adrenal medulla.

• Journal of Microbiology and Biotechnology
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• v.30 no.11
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• pp.1626-1639
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• 2020

In Caenorhabditis elegans, SHN-1 is the homologue of SHANK, a scaffolding protein. In this study, we determined the molecular basis for SHN-1/SHANK in the regulation of innate immune response to fungal infection. Mutation of shn-1 increased the susceptibility to Candida albicans infection and suppressed the innate immune response. After C. albicans infection for 6, 12, or 24 h, both transcriptional expression of shn-1 and SHN-1::GFP expression were increased, implying that the activated SHN-1 may mediate a protection mechanism for C. elegans against the adverse effects from fungal infection. SHN-1 acted in both the neurons and the intestine to regulate the innate immune response to fungal infection. In the neurons, GLR-1, an AMPA ionotropic glutamate receptor, was identified as the downstream target in the regulation of innate immune response to fungal infection. GLR-1 further positively affected the function of SER-7-mediated serotonin signaling and antagonized the function of DAT-1-mediated dopamine signaling in the regulation of innate immune response to fungal infection. Our study suggests the novel function of SHN-1/SHANK in the regulation of innate immune response to fungal infection. Moreover, our results also denote the crucial role of neurotransmitter signals in mediating the function of SHN-1/SHANK in regulating innate immune response to fungal infection.