• Anxiety and mood
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• v.7 no.1
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• pp.34-39
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• 2011

Objectives : An early age at onset of obsessive compulsive symptoms in family studies has been strongly associated with a more familial form of obsessive compulsive disorder (OCD). Further, many reports have suggested that early- and late- onset OCD represent separate subtypes of the disorder. The aim of this study was to investigate the associations between the glutamate receptor, the ionotropic, n-methyl-d-aspartate (NMDA) subunit 2B gene (GRIN2B) polymorphisms, and onset of OCD in the Korean population. Methods : We recruited 109 OCD patients and classified them into early- (age of onset <18 years) and late-onset groups (age of onset${\geq}$18). Genomic DNA was extracted from their blood after which the genotypes and allelic frequencies of the two GRIN2B polymorphisms (5072T/G and 5988T/C) were compared in the two groups. We also compared genetic data between child- (age of onset${\leq}$15) and adult-onset groups (age of onset${\geq}$19) using the same protocol. Results : There were no significant differences between the early- and late-onset groups with respect to genotype. Moreover, we could not find any differences in genotype frequencies between child and adult-onset groups. Conclusions : Our study suggested that GRIN2B polymorphisms (5072T/G and 5988T/C) do not affect the onset of OCD in Koreans. However, this finding has resulted from a preliminary study and thus, further study is required.

• Korean Journal of Acupuncture
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• v.36 no.2
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• pp.93-103
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• 2019

Objectives : The aim of this study is to review the current trends in experimental studies on the acupuncture moxibustion treatment for visceral hypersensitivity. Methods : PubMed was searched for experimental studies about visceral hypersensitivity and acupuncture/moxibustion. Data were extracted and tabulated from the selected articles about experimental method, intervention, result and mechanism. Results : Total 23 articles were reviewed. Chronic visceral hypersensitivity animal model was applied in 17 studies (74%). Visceral hypersensitivity was measured by abdominal withdrawal reflex scoring or/and abdominal electromyogram. Acupoints like ST25, ST36, ST37, BL25, LI11, BL32 and PC6 were treated by electroacupuncture or moxibustion. All articles reported that electroacupuncture or moxibustion treatment is significantly effective in reducing visceral hypersensitivity. Treatment mechanisms were studied, related to mast cell, serotonin (5-HT) and receptor (5-HT3R and 5-HT4R), substance P (SP), vasoactive intestinal polypeptide (VIP), c-fos positive cell, corticotropin-releasing hormone (CRH), purinergic 2X (P2X)2, P2X3, P2X4, P2X7, N-methyl-D-aspartate (NMDA) receptor (NR1 and NR2B), prokinectin (PK) 1 and PK2. Conclusions : Evidences on acupuncture/moxibustion treatment for visceral hypersensitivity in animal studies warrant more research on effective acupoins, electro-acupuncture methods and treatment durations.

• The Journal of Internal Korean Medicine
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• v.44 no.6
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• pp.1337-1345
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• 2023

Objectives: This study reports on the improvement of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis with ovarian teratoma after Korean medicine treatment. Methods: A patient was treated with Korean medicine treatments, such as acupuncture and herbal medications (Gami-ondam-tang and Samulanshin-tang-gamibang). The patient's improvement was evaluated using manual muscle testing (MMT), the Mini-Mental State Exam-Korea (MMSE-K), the modified Barthel index (MBI), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Results: After using Korean medicine treatments, the patient's MMT, MMSE-K, and MBI scores increased, and the CASE score decreased. Conclusion: This case suggests that Korean medicine can be effective in treating the symptoms of anti-NMDA receptor encephalitis.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.19-29
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• 1996

The neurological manifestations of AIDS include dementia, encountered even in the absence of opportunistic superinfection or malignancy. The AIDS Dementia Complex appears to be associated with several neuropathological abnormalities, including astrogliosis and neuronal injury or loss. How can HIV-1 result in neuronal damage if neurons themselves are only rarely, if ever, infected by the vitus\ulcorner In vitro experiments from several different laboratiories have lent support to the existence of HIV- and immune-related toxins. In one recently defined pathway to neuronal injury, HIV-infected macrophages/microglia as well as macrophages activated by HIV-1 envelope protein gp120 appear to secrete excitants/neurotoxins. These substances may include arachidonic acid, platelet-activating factor, free radicals (NO - and O$_2$), glutamate, quinolinate, cysteine, cytokines (TNF-${\alpha}$, IL1-B, IL-6), and as yet unidentified factors emanating from stimulated macrophages and possibly reactive astrocytes. A final common pathway for newonal suscepubility appears to be operative, similar to that observed in stroke, trauma, epilepsy, and several neurodegenerative diseases, including Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This mechanism involves excessive activation of N-methyl-D-aspartate (NMDA) receptor-operated channels, with resultant excessive influx of Ca$\^$2+/ leading to neuronal damage, and thus offers hope for future pharmacological intervention. This chapter reviews two clinically-tolerated NMDA antagonists, memantine and nitroglycerin; (ⅰ) Memantine is an open-channel blocker of the NMDA-associated ion channel and a close congener of the anti-viral and anti-parkinsonian drug amantadine. Memantine blocks the effects of escalating levels of excitotoxins to a greater degree than lower (piysiological) levels of these excitatory amino acids, thus sparing to some extent normal neuronal function. (ⅱ) Niuoglycerin acts at a redox modulatory site of the NMDA receptor/complex to downregulate its activity. The neuroprotective action of nitroglycerin at this site is mediated by n chemical species related to nitric oxide, but in a higher oxidation state, resulting in transfer of an NO group to a critical cysteine on the NMDA receptor. Because of the clinical safety of these drugs, they have the potential for trials in humans. As the structural basis for redox modulation is further elucidated, it may become possible to design even better redox reactive reagents of chinical value. To this end, redox modulatory sites of NMDA receptors have begun to be characterized at a molecular level using site-directed mutagenesis of recombinant subunits (NMDAR1, NMDAR2A-D). Two types of redox modulation can be distinguished. The first type gives rise to a persistent change in the functional activity of the receptor, and we have identified two cysteine residues on the NMDARI subunit (#744 and #798) that are responsible for this action. A second site, presumably also a cysteine(s) because <1 mM N-ethylmaleimide can block its effect in native neurons, underlies the other, more transient redox action. It appears to be at this, as yet unidentified, site on the NMDA receptor that the NO group acts, at least in recombinant receptors.

• 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.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.2
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• pp.43-49
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• 2008

Flavonoids have been shown to affect calcium signaling in neurons. However, there are no reports on the effect of apigenin on glutamate-induced calcium signaling in neurons. We investigated whether apigenin affects glutamate-induced increase of free intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in cultured rat hippocampal neurons, using fura-2-based digital calcium imaging and microfluorimetry. The hippocampal neurons were used between 10 and 13 days in culture from embryonic day 18 rats. Pretreatment of the cells with apigenin ($1{\mu}M$ to $100{\mu}M$) for 5 min inhibited glutamate ($100{\mu}M$, 1 min) induced $[Ca^{2+}]_i$ increase, concentration-dependently. Pretreatment with apigenin ($30{\mu}M$) for 5 min significantly decreased the $[Ca^{2+}]_i$ responses induced by two ionotropic glutamate receptor agonists, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA, $10{\mu}M$, 1 min) and N-methyl-D-aspartate (NMDA, $100{\mu}M$, 1 min), and significantly inhibited the AMPA-induced peak currents. Treatment with apigenin also significantly inhibited the $[Ca^{2+}]_i$ response induced by 50 mM KCl solution, decreased the $[Ca^{2+}]_i$ responses induced by the metabotropic glutamate receptor agonist, (S)-3,5-dihydroxy-phenylglycine (DHPG, 100 $[Ca^{2+}]_i$, 90 s), and inhibited the caffeine (10 mM, 2 min)-induced $[Ca^{2+}]_i$ responses. Furthermore, treatment with apigenin ($30{\mu}M$) significantly inhibited the amplitude and frequency of 0.1 mM $[Mg^{2+}]_o$-induced $[Ca^{2+}]_i$ spikes. These data together suggest that apigenin inhibits glutamate-induced calcium signaling in cultured rat hippocampal neurons.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.164-174
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• 2000

Background: After an injury to tissue such as the skin, hyperalgesia develops. Hyperalgesia is characterized by an increase in the magnitude of pain evoked by noxious stimuli. It has been postulated that in the mechanism of hyperalgesia (especially secondary hyperalgesia) and allodynia, a sensitization of central nervous system such as spinal dorsal horn may contribute to development of hyperalgesia. However, the precise mechanism is still unclear. In the present study, we investigated the roles of N-methyl-D-aspartate (NMDA) receptor and nitric oxide (NO) system in the mechanism of hyperalgesia, and their relations with c-fos expression Methods: Inflammation was induced by injection of complete Freund adjuvant (CFA) into unilateral hindpaw of Sprague-Dawley rat. Behavioral studies measuring paw withdrawal responses by von Frey filaments and paw withdrawal latencies by radiant heat stimuli and stainings of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and c-fos immunoreactivity were performed. The effects of MK-801, an NMDA receptor blocker and $N^\omega$-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor were evaluated. Results: 1) Injection of CFA induced mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia. And it increased the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 2) MK-801 inhibited mechanical hyperalgesia and thermal hyperalgesia induced by CFA and reduced the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 3) L-NNA inhibited the thermal hyperalgesia and reduced the number of NADPH-diaphorase positive neurons, but did not affect the number of c-fos expression neurons. Conclusions: These results suggest that in the mechanism of mechanical hyperalgesia, NMDA receptor but not NO-system is involved and in the case of thermal hyperalgesia both NMDA receptor and NO system are involved. NO system did not affect the expression of c-fos, but c-fos expression and NOS activity were dependent on the activity of NMDA receptor.

• Archives of Pharmacal Research
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• v.24 no.1
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• pp.64-68
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• 2001

Endothelin-1 (ET-1 ), a novel and potent vasoconstrictor in blood vessel, is known to have some functions in the rat central nervous system (CNS), In order to investigate the central functions of ET-1 , ET-1 was administered to the periaqueductal gray area (PAC) of anesthetized rats to induce barrel rolling and increase the arterial blood pressure (ABP). ET-1 had a modulatory effect on central cardiovascular and behavioral control. The selective N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (3${u}m/ol/kg$, i.p.) blocked the ET-1 induced responses, and both the nitric oxide synthase (NOS) inhibitor L-NAME (N-nitro-L-arginine mIThyl-ester 1 nmol/rat) and the nitric oxide (NO) scavenger hemoglobin (15 nmol/rat) had similar effects in redtAcing the IT-1 (10 pmol/rat)-induced behavioral changes and ABP elevation. However, NO donor sodium nitroprusside (SNP 10${u}g$, 1${u}g/rat$) decreased the ET-1 induced ABP elevation, and recovered the ET-1 -induced barrel rolling effect that was reduced by MK-801. These results suggest that ET-1 might have neuromodulatory functions such as ABP elevation and barrel rolling induction in the PAG of the rats via the NMDA receptor and NO.

• Journal of Ginseng Research
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• v.24 no.4
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• pp.196-201
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• 2000

Effects of ginsenosides on NaCN-induced neuronal cell death were studied in cultured rat cerebellar granule cells. NaCN produced a concentration-dependent (1-10 mM) reduction of cell viability (measured by frypan blue exclusion test), that was blocked by N-methyl-D-aspartate receptor antagonist (MK-801) and L-type Ca$\^$2+/ channel blocker (verapamil). Pretreatment with ginsenosides (Rb$_1$, Rc, Re, Rf and Rg$_1$) significantly decreased the neuronal cell death in a concentration range of 0.5∼5$\mu\textrm{g}$/ml. Ginsenosides Rb$_1$ and Rc (5 $\mu\textrm{g}$/ml) inhibited glutamate release into medium induced by NaCN (5 mM). NaCN (1 mM)-induced increase of [Ca$\^$2+/], was significantly inhibited by the pretreatment of Rb$_1$ and Rc (5 $\mu\textrm{g}$/ml). Other ginsenosides caused relatively little inhibition on the elevation of glutamate release and of (Ca$\^$2+/). These results suggest that the NaCN-induced neurotoxicity was related to a series of cell responses consisting of glutamate release and [Ca$\^$2+/]i elevation via glutamate (NMDA and kainate) receptors and resultant cell death, and that ginsenosides, especially Rb$_1$ and Rc, prevented the neuronal cell death by the blockade of the NaCN-induced Ca$\^$2+/influx.

• Journal of Ginseng Research
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• v.23 no.1 s.53
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• pp.38-43
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• 1999

Ginseng total saponins (ginsenosides) are biologically active main ingredients of Panax ginseng. In present study, we have investigated whether pretreatment of ginsenosides inhibited capsaicin-induced pain at the spinal level, in the view that capsaicin causes substance P (SP) release from primary afferents. Ginsenosides relieved capsaicin-induced pain in a dose-dependent manner. The $ED_{50}$ of the effect was 43 (20-93, $95\%$ C.I.) ${\mu}g/mouse$. We investigated excitatory amino acids-induced nociceptive responses in mice, because these agents are also involved in nociceptive transmission in the spinal cord. Coadministration of ginsenosides with N-methyl-D-aspartate (NMDA) or kainate via i.t. inhibited NMDA- but not kainate-induced pain behaviors. The $ED_{50}$ for the inhibition of NMDA-induced pain by ginsenosides was 37 (21-66, $95\%$ C.I.) ${\mu}g/mouse$. These results suggest that the ginsenosides-induced antinociception results from blocking of pain transmitter-induced nociceptive information at the spinal level.