• The Korean Journal of Physiology and Pharmacology
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• v.5 no.2
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• pp.189-197
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• 2001

To investigate propofol's effects on ionic currents induced by ${\gamma}-aminobutyric$ acid (GABA) and glycine as well as on those produced by the nicotinic acetylcholine- and glutamate-responsive channels, rat dorsal raphe neurons were acutely dissociated and the nystatin-perforated patch-clamp technique under voltage-clamp conditions was used to observe their responses to the administration of propofol. Propofol evoked ion currents in a dose-dependent manner, and propofol $(10^{-4}\;M)$ was used to elicit ion currents through the activation of $GABA_A,$ glycine, nicotinic acetylcholine and glutamate receptors. Propofol at a clinically relevant concentration $(10^{-5}\;M)$ potentiated $GABA_A-,$ glycine- and NMDA receptor-mediated currents. The potentiating action of propofol on $GABA_A-,$ glycine- and NMDA receptor-mediated responses involved neither opioid receptors nor G-proteins. Apparently, propofol modulates inhibitory and excitatory neurotransmitter-activated ion channels either by acting directly on the receptors or by potentiating the effects of the neurotransmitters, and this modulation appears to be responsible for the majority of the anaesthetic and/or adverse effects.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.303-307
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• 2006

The effects of ethanol on corticostriatal synaptic transmission were examined, using extracellular recording and analysis of population spike amplitudes in rat brain slices, to study how acute ethanol intoxication impairs striatal function. Ethanol caused a decrease in population spike amplitudes in a dose dependent manner ($50{\sim}200mM$). Pretreatment with picrotoxin, a ${\gamma}-amino$ butyric acid $(GABA)_{A}$ receptor antagonist, increased the population spikes but ethanol (100 mM) was still effective in decreasing the population spikes under this condition. In the presence of $_{(DL)}-2-amino-5-phosphonovaleric$ acid (APV), N-methyl-D-aspartate (NMDA) receptor antagonist, the inhibitory action of ethanol on population spikes was not shown. These results suggest that ethanol inhibits the glutamatergic corticostriatal synaptic transmission through blockade of NMDA receptors.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.30 no.3
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• pp.127-131
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• 2019

Many neurologic disorders manifest as psychiatric symptoms. Anti-N-Methyl-D-Aspartate (NMDA) receptor encephalitis is an autoimmune disease of the brain characterized by numerous neurological and psychiatric features. Despite being rare, its prevalence is rapidly increasing and early management is critical in ensuring successful and sustainable recovery. Therefore, the illness should be considered as a differential diagnosis when clinically assessing patients. This report presents a case of a female child who was hospitalized for acute psychiatric manifestations, which was later confirmed as anti-NMDA receptor encephalitis. She recovered relatively successfully after combined neurological and psychiatric treatment. This report provides information on the clinical course of early onset anti-NMDA receptor encephalitis, including treatment strategy and prognosis.

• The Korean Journal of Pain
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• v.24 no.1
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• pp.53-56
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• 2011

Although postherpetic neuralgia (PHN) is a common chronic pain syndrome, the pathophysiology of this disorder is not well known and management is often very difficult. N-methyl-D-Aspartate (NMDA) receptor antagonists are known to be effective in PHN, and magnesium, a physiological blocker of NMDA receptors, is widely used to treat various chronic pain disorders. Here, we present a case of the PHN refractory to conventional treatment, which was treated successfully with transforaminal epidural injection of magnesium sulphate at the affected dermatome.

• Proceedings of the Ginseng society Conference
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• 2005.11a
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• pp.32-40
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• 2005

The last two decades have shown a marked expansion in publications of diverse effects of Panax ginseng. Ginsenosides, as active ingredients of Panax ginseng, are saponins found in only ginseng. Recently, a line of evidences shows that ginsenosides regulate various types of ion channel activity such as Ca$^{2+}$, K$^+$, Na$^+$, Cl$^-$, or ligand gated ion channels (i.e. 5-HT$_3$, nicotinic acetylcholine, or NMDA receptor) in neuronal, non-neuronal cells, and heterologously expressed cells. Ginsenosides inhibit voltage-dependent Ca$^{2+}$, K$^+$, and Na$^+$ channels, whereas ginsenosides activate Ca$^{2+}$-activated Cl$^-$ and Ca$^{2+}$-activated K$^+$ channels. Ginsenosides also inhibit excitatory ligand-gated ion channels such as 5-HT$_3$. nicotinic acetylcholine, and NMDA receptors. This presentation will introduce recent findings on the ginsenoside-induced differential regulations of ion channel activities as a ligand as other drugs do.

• The Journal of Pediatrics of Korean Medicine
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• v.15 no.1
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• pp.77-104
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• 2001

The effects of the oriental herbal medicine Saenghyetang(SHT, 生慧湯), which consists of Rehmanniae Radix (熟地黃 九蒸: was made by 9th steam) 40g, Corni Fructus(山茱黃) 16g, Polygalae Radix(遠志) 8g, Zizyphi Spinosae Semen(酸棗仁) 2g, Biotae Semen(柏子仁 去油: oil ingredient was removed) 20g, Poria Cocos(茯笭) 12g, Ginseng Radix(人蔘) 12g, Acori Graminei Rhizoma(石菖蒲) 2g, Sinapis Semen(白芥子) 8g, on learning ability and memory were investigated. Hot water extract(HWE) and ethanol extract(EE) from SHT were used for the studies. Learning ability and memory are related to modifications of synaptic strength among neurons that interactive. Enhanced synaptic coincidence detection leads to improved learning ability and memory. If the NMDA receptor, a synaptic coincidence detector, acts as a graded switch for memory formations, enhanced signal detection by NMDA receptors should enhance learning ability and memory. It was shown that NR2B was increased in the forebrains of oriental medicine-administrated mice, leading to enhanced activation of NMDA receptors and facilitating synaptic potentiation in response to stimulation at 10-100 Hz. These HWE-SHT treated mice exhibited that superior ability in learning and memory when performing various behavioral tasks, showing that NR2B is enhanced by HWE-SHT treatment and also is critical in gating the age-dependent threshold for plasticity and memory formation. NMDA receptor-dependent modifications, which were mediated in part by HWE administration, of synaptic efficacy, therefore, represent a mechanism for associative learning ability and memory. Results suggest that oriental medical enhancement of NR2B contributes to increase intelligence and memory in mammals On the other hand, to examine the effects of EE-SHT on the learning ability and memory in experimental mice, EE-SHT was tested on passive and active avoidance responses. The EE-SHT ameliorated the memory retrieval deficit induced by ethanol in mice, but not other memory impairments. EE-SHT(10, 20mg/100 g, p.o.) did not affect the passive avoidance responses of normal mice in the step through and step down tests, the conditioned and unconditioned avoidance responses of normal mice in the shuttle box, lever press performance tests and the ambulatory activity of normal mice in a normal condition. However, EE-SHT at 20 mg/kg significantly decrease the spontaneous motor activity during the shuttle box test, and also to extend the sleeping time induced by pentobarbital in mice. These results suggest that SHT has an ameliorating effect on memory retrieval impairments and a weak tranquilizing action.

• Journal of Ginseng Research
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• v.35 no.2
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• pp.219-225
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• 2011

Korean red ginseng (KRG) is a valuable and important traditional medicine in East Asian countries and is currently used extensively for botanical products in the world. KRG has both stimulatory and inhibitory effects on the central nervous system (CNS) suggesting its complicated action mechanisms. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Some studies reported that KRG has antinociceptive effects, but there are few reports of the functional studies of KRG on the SG neurons of the Vc. In this study, a whole cell patch clamp study was performed to examine the action mechanism of a KRG extract on the SG neurons of the Vc from juvenile mice. KRG induced short-lived and repeatable inward currents on all the SG neurons tested in the high chloride pipette solution. The KRG-induced inward currents were concentration dependent and were maintained in the presence of tetrodotoxin, a voltage gated $Na^+$ channel blocker. The KRG-induced inward currents were suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist and/or picrotoxin, a gamma-aminobutyric acid $(GABA)_A$ receptor antagonist. However, the inward currents were not suppressed by d,l-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. These results show that KRG has excitatory effects on the SG neurons of the Vc via the activation of non-NMDA glutamate receptor as well as an inhibitory effect by activation of the $GABA_A$ receptor, indicating the KRG has both stimulatory and inhibitory effects on the CNS. In addition, KRG may be a potential target for modulating orofacial pain processing.

• Molecules and Cells
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• v.37 no.4
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• pp.345-355
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• 2014

Mitigating secondary delayed neuronal injury has been a therapeutic strategy for minimizing neurological symptoms after several types of brain injury. Interestingly, secondary neuronal loss appeared to be closely related to functional loss and/or death of astrocytes. In the brain damage induced by agonists of two glutamate receptors, N-ethyl-D-aspartic acid (NMDA) and kainic acid (KA), NMDA induced neuronal death within 3 h, but did not increase further thereafter. However, in the KA-injected brain, neuronal death was not obviously detectable even at injection sites at 3 h, but extensively increased to encompass the entire hemisphere at 7 days. Brain inflammation, a possible cause of secondary neuronal damage, showed little differences between the two models. Importantly, however, astrocyte behavior was completely different. In the NMDA-injected cortex, the loss of glial fibrillary acidic protein-expressing ($GFAP^+$) astrocytes was confined to the injection site until 7 days after the injection, and astrocytes around the damage sites showed extensive gliosis and appeared to isolate the damage sites. In contrast, in the KA-injected brain, $GFAP^+$ astrocytes, like neurons, slowly, but progressively, disappeared across the entire hemisphere. Other markers of astrocytes, including $S100{\beta}$, glutamate transporter EAAT2, the potassium channel Kir4.1 and glutamine synthase, showed patterns similar to that of GFAP in both NMDA- and KA-injected cortexes. More importantly, astrocyte disappearance and/or functional loss preceded neuronal death in the KA-injected brain. Taken together, these results suggest that loss of astrocyte support to neurons may be a critical cause of delayed neuronal death in the injured brain.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1672-1677
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• 2006

Sarcodon aspratus is the mushroom of Telephoracea which was been classified into Alphllophorales. The aqueous extract of Sarcodon aspratus in known to have anti-tumor activity, immune modulatory effect, and anti-oxidative action. The descending pain control system consists of three major components: the periaqueductal gray (PAG) of the midbrain, the rostroventral medulla including the nucleus raphe magnus, and the spinal dorsal horn. Glutamate is the primary excitatory neurotransmitter in the brain. Glutamate ionotropic receptors are classified as N-methyl-D-aspartate (NMDA) receptor, ${\alpha}$-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor, and kainate receptor. In the present study, the modulation of Sarcodon aspratus on the ion currents activated by glutamate, NMDA, AMPA, and kainate in the acutely dissociated PAG neurons was investigated by nystatin-perforated patch-clamp technique under boltage-clamp condition. Sarcodon aspratus increased glutamate- and NMDA-induced ion currents were not increased by Sarcodon aspratus. The present results show that Sarcodon aspratus may activate the descending pain control system in rat PAG neurons through NMDA receptor.

• Journal of Life Science
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• v.32 no.1
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• pp.11-22
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• 2022

N-methyl-D-aspartate (NMDA) receptors have received considerable attention regarding their involvement in glutamate-induced neuronal excitotoxicity. Resveratrol has been shown to exhibit neuroprotective effects against this kind of overactivation, but the underlying cellular mechanisms are not yet clearly understood. In this study, HT-22 neuronal cells were treated with NMDA in Mg²⁺-free buffer and subsequently used as an experimental model of glutamate excitotoxicity to elucidate the mechanisms of resveratrol-induced neuroprotection. We found that NMDA treatment causes a drop in MTT reduction ability, disrupts inside-negative transmembrane potential of mitochondria, depletes cellular ATP levels, and stimulates intracellular ROS production. Double fluorescence imaging studies demonstrated an increased formation of mitochondrial permeability transition (MPT) pores accompanied by apoptotic cell death, while cobalt protoporphyrin and bilirubin showed protective effects against NMDA-induced mitochondrial injury. On the other hand, zinc protoporphyrin IX significantly attenuated the protective effects of resveratrol which was itself shown to enhance heme oxygenase-1 (HO-1) mRNA and protein expression levels. In cells transfected with HO-1 small interfering RNA, resveratrol failed to suppress the NMDA-induced effects on MTT reduction ability and MPT pore formation. The present study suggests that resveratrol may prevent mitochondrial injury in NMDA- treated HT-22 cells and that enhanced expression of HO-1 is involved in the underlying cellular mechanism.