• Title, Summary, Keyword: NMDA수용체

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Effect of N-methyl-D-aspartic acid(NMDA)-and Non NMDA-Receptor Agonists on Serotonin Release from Cultured Neurons of Fetal Rat Brainstem (뇌간 신경세포 배양에서 세로토닌 분비에 대한 N-methyl-D-aspartic Acid(NMDA) 및 Non-NMDA 수용체 효현제들의 작용)

  • Yoo, Soon-Mi;Kim, Yul-A;Song, Dong-Keun;Suh, Hong-Won;Kim, Yung-Hi
    • The Korean Journal of Pharmacology
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    • v.31 no.2
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    • pp.141-144
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    • 1995
  • Serotonergic neurons in brainstem play important roles in the endogenous descending pain inhibitory system. To illucidate the involvement of glutamate receptors in the regulation of brainstem serotonergic neurons, we studied the effects of glutamate receptor agonists on 5-hydroxytryptamine(5-HT) release from cultured neurons of rat fetal (gestational age 14th day) brainstem. Cultured cells maintained for 10 days in vitro were stimulated for 30 minutes with agonists of glutamate receptor subtypes at 10-1,000 micromolar concentration. Glutamate (10-1,000 M) increased 5-HT release in a concentration-dependent manner. N-methyl-D-aspartic acid $(NMDA)(10-1,000\;{\mu}M)$ increased 5-HT release in a concentration-dependent manner. Non-NMDA receptor agonists, kainate and $AMPA(3-1,000\;{\mu}M)$ also concentration-dependently increased 5-HT release. These results suggest that both NMDA and non-NMDA receptors regulate 5-HT release from brainstem serotonergic neurons.

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The Role of NMDA Receptor in Learning and Memory (학습과 기억에서 NMDA 수용체의 역할)

  • Kim, Seung-Hyun;Shin, Kyung-Ho
    • Sleep Medicine and Psychophysiology
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    • v.7 no.1
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    • pp.10-17
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    • 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.

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Synaptic Pattern of NMDA R1 upon the Direction-Selective Retinal Ganglion Cells in Developing Mouse Retina (발생 중 마우스 망막에서 방향특이성 신경절세포의 NMDA R1 수용체의 시냅스 패턴)

  • Lee, Jee-Geon;Kwon, Oh-Ju;Jeon, Chang-Jin
    • 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.

NMDA, quisqualate 및 kainate에 의하여 유발된 신경독성에 미치는 betaine의 효과

  • 박미정;김소라;김영중
    • Proceedings of the Korean Society of Applied Pharmacology
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    • pp.239-239
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    • 1994
  • 신경쇠약의 치료로 상용하며, 빈혈의 치료와 예방의 효과가 있으며, 노화방지에 도움이 되어 민간약으로는 장수(長壽)약으로 꼽히고 있는 구기자가 글루타메이트에 의한 신경독성을 차단하며, 이러한 효과는 구기자의 성분 중 betaine에 의하여 나타난다. Betaine이 어떠한 작용 기전에 의하여 글루타메이트에 의한 신경독성을 차단하는 지를 밝히기 위하여 글루타메이트가 작용하는 각기 다른 수용체인 NHDA 및 non-NMDA 수용체에 어떻게 작용하는 지를 알아보았다. 각 수용체의 선택적인 효능제인 NMDA, kainate 및 quisqualate 각각을 사용하여 인위적으로 독성을 유도시킨 후 이에 대한 betaine의 작용을 알아 본 결과 betaine은 quisqualate에 의하여 유도된 신경독성에서 모두 유사한 정도의 효과를 나타내었다. 이러한 효과는 betaine과 구조가 유사한 glycine의 다른 구조 유사체인 dimethylglycine이나 sarcosine과는 다른 작용양상을 나타내는 것이다. Dimethylglycine과 sarcosine은 kainate에 의한 독성에 대하여 미약한 효과를 나타냈으나, NMDA에 의한 독성에는 정상대조군의 LDH 값의 50% 이상에까지 이르게하는 효과를 나타내는 것으로 보아 이들이 NMDA에 의한 신경독성을 효과적으로 차단한다는 것을 암시해 준다고 할 수 있다. 그러나 betaine의 글루타메이트에 의한 신경독성을 차단하는 효과는 다른 glycine 구조 유사체처럼 glycine과 경쟁적으로 작용하여 나타나는 결과는 아니라고 여겨진다. 또한 글루타메이트에 의한 신경독성이 일어나는 기전 중의 하나가 calcium 이온의 세포내의 과도한 유입으로 인한 것으로 알려져 있으나 세포내의 calcium 이온의 양을 측정하여 본 결과 betaine은 글루타메이트로 인한 세포내 calcium 이온의 증가에 대하여 별다른 효과를 나타내지 않았다. 따라서 betaine의 글루타메이트에 의한 신경독성 차단 효과는 이미 미생물에서 보고된 바 있는 betaine의 세포내 삼투압에 대한 보호작용이나 항산화작용과 관련된 기전에 의하여 나타나는 것일 가능성이 높은 것으로 추측되어진다.

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Distribution of Glutamate Receptors in the Retina of the Greater Horseshoe Bat (Rhinolophus ferrumequinum) (한국관박쥐 망막에서 글루타메이트 수용체의 분포 양상)

  • Kwon, Oh-Ju;Jeon, Chang-Jin
    • Journal of Korean Ophthalmic Optics Society
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    • v.19 no.3
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    • pp.413-418
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    • 2014
  • Purpose: The objective of this study was analyzing the distribution of the excitatory neurotransmitter glutamate receptor to investigate the function in the retina of the greater horseshoe bat. Methods: After retinal tissues of adult greater horseshoe bat were cut into $40{\mu}m$ vertical sections, standard immuno-cytochemical techniques was applied for analysis. Immunofluorescence images were obtained using the Bio-Rad MRC 1024 laser scanning confocal microscope. Results: AMPA (GluR1-4), Kainate (GluR5-7, KA1-2) and NMDA (1, 2A, 2B) mainly distributed in the inner plexiform layer and outer plexiform layer. KA1 receptors have existed not only plexiform layer but also ganglion cell layer. Conclusions: The greater horseshoe bat has same neuron and neurotransmitter to mammalian retina. These findings suggest that bat has a functional retina for visual analysis.

The Effect of Topiramate on Hippocampal Neuronal Death and Expression of Glutamate Receptor in Kainate-induced Status Epilepticus Model (Kainate 유발 간질중첩증 모델에서 topiramate가 해마 신경세포사와 glutamate 수용체 발현에 미치는 영향)

  • Park Min-Jeong;Ha Se-Un;Bae Hae-Rahn;Kim Sang-Ho
    • Journal of Life Science
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    • v.15 no.3
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    • pp.505-512
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    • 2005
  • Excitotoxicity and epileptogenesis have often been associated with glutamate receptor activation. Accumulating evidences indicates that topiramate (TPM), an antiepileptic drug with multiple mechanisms of action has neuroprotective activity. We explored the neuroprotective effect of TPM on the status epilepticus (SE)-induced hippocampal neuronal death. After development of SE by kainite injection (15 mg/Kg), rats were treated with TPM (10mg/kg) for 1 week. The neuronal death was detected by Apop tag in situ detection kit, and the expression levels of glutamate receptors were semi-quantitatively analyzed by immunoblot. Kainate-induced SE caused a significant neuronal death and cell loss in CAI and CA3 regions of hippocampus at 1 week. However, treatment of TPM for 1 week after SE markedly reduced hippocampal neuronal death. The expression of N-methyl-D-aspartate (NMDA) receptor subunit 1, was increased by SE, but was not affected by 1 week treatment of TPM. The expressions of NMDA receptor subunit 2a and 2b were not changed by either SE or TPM. As for ${\alpha}-amino-3-hydroxy-5-methyl-4-isoxazole-propionate$ (AMPA) glutamate receptors (GluR), kainate-induced SE markedly up-regulated GluR1 expression but down-regulated GluR2 expression, leading to increased formation of $Ca^{2+}$ permeable GluR2- lacking AMPA receptors. TPM administration for 1 week attenuated SE-induced expression of both the up-regulation of GluR1 and down-regulation of GluR2, reversing the ratio of GluR1/GluR2 to the control value. In conclusion, TPM protects neuronal cell death against glutamate induced excitotoxicity in kainate-induced SE model, supporting the potential of TPM as a neuroprotective agent.

Other N-Methyl-D-Aspartate (NMDA) Receptor Antagonists with a Rapid Onset of Action and Less Side Effect in the Treatment of Depression (우울증 치료에서 빠른 효과와 적은 부작용을 가진 새로운 N-Methyl-D-Aspartate(NMDA) 수용체 길항제)

  • Choi, Bum-Sung;Lee, Hwa-Young
    • Korean Journal of Biological Psychiatry
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    • v.22 no.4
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    • pp.149-154
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    • 2015
  • Mood disorder is a common psychiatric illness with a high lifetime prevalence in the general population. Many prescribed antidepressants modulate monoamine neurotransmitters including serotonin, norepinephrine and dopamine. There has been greater focus on the major excitatory neurotransmitter in the human brain, glutamate, in the pathophysiology and treatment of major depressive disorder (MDD). Recently, ketamine, an N-methyl-D-aspartate receptor antagonist, has received attention and has been investigated for clinical trials and neurobiological studies. In this article, we will review the clinical evidence for glutamatergic dysfunction in MDD, the progress with ketamine as a rapidly acting antidepressant, and other N-methyl-D-aspartate receptor antagonist for treatment-resistant depression.

Glutamate-Induced Serotonin Depletion in Fetal Rat Brainstem Cultures (흰쥐태 뇌간의 배양에서 Glutamate에 의한 Serotonin의 고갈)

  • Park, Sang-Wook;Wie, Myung-Bok;Song, Dong-Keun;Kim, Yong-Sik;Kim, Yung-Hi
    • The Korean Journal of Pharmacology
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    • v.29 no.2
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    • pp.189-193
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    • 1993
  • Exposure of dissociated cultures from fetal rat brainstem to glutamate for upto 6 h decreased cellular contents of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in a concentration- and time-dependent manner. In addition, glutamate induced lactate dehydrogenase leakage. Tetrodotoxin did not block the effects induced by glutamate. MK-801 $(1{\mu}M)$, an N-methyl-D-aspartate (NMDA) channel blocker, but not 6-cyano-2,3-dihydroxy-7-nitro-quinoxazoline $(CNQX;\;3{\mu}M)$, a non-NMDA receptor antagonist, blocked glutamate-induced effects, indicating that these glutamate-induced responses are mediated through NMDA receptors.

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Effect of N-Methyl-D-Aspartate Glutamate Receptor Antagonist, Memantine, on Alcohol Intake in C57BL/6 Mice (N-methyl-D-aspartate glutamate 수용체 길항제 memantine의 투여가 C57BL/6형 생쥐의 알코올 섭취량에 미치는 영향)

  • Kim, Hyeun-Kyeung;Kim, Sung-Gon;Kim, Ji-Hoon;Shin, Su-Mi;Lee, Sang-Shin;Bae, So-Hyun;Kim, Ho-Chan
    • Journal of Life Science
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    • v.19 no.4
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    • pp.532-537
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    • 2009
  • Previous studies reported that the N-methyl-D-aspartate (NMDA) receptor is related to alcohol dependence in terms of developing withdrawal or tolerance, however, it is controversial whether NMDA receptor antagonists are effective in preventing relapse in alcohol-dependent patients or not. The purpose of this study was to investigate the effect of memantine, an NMDA receptor antagonist, on alcohol intake in C57BL/6 mice, which prefer drinking hereditarily. Using limited access procedures in C57BL/6 mice in the state of alcohol dependence, vehicle, naltrexone 1.0 mg/kg or, memantine 5, 25, or 50 mg/kg i.p. was administered respectively for twelve days. Medication effects on 2-hours alcohol, 22-hour water, and 24-hour food intake and body weight were studied. Using repeated measure ANOVA, the naltrexone 1 mg/kg, memantine 5, 25, or 50 mg/kg, and vehicle groups showed significant medication by day interaction (naltrexone, df=4, F=11.827, p<0.01, memantine 5 mg/kg, df=4, F=7.999, p<0.01; memantine 25 mg/kg, df=4, F=6.199, p<0.05; memantine 50 mg/kg, df=4, F=10.522, p<0.01) in 2-hour alcohol intake. In 3 memantine groups, there was no significant medication by day interaction with the vehicle group in 22-hour water intake, 24-hour food intake, or body weight. The naltrexone and vehicle groups showed significant medication by day interaction in body weight, but not in 22-hour water or 24-hour food intake. From these results, it is suggested that memantine treatment can affect alcohol intake in mice. Therefore, it is possible that a pure NMDA receptor antagonist is effective in preventing relapse in alcohol-dependent patients.