• 대한임상독성학회지
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• 제19권2호
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• pp.100-109
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• 2021

Purpose: The purpose of this study was to investigate effect of N-acetylcysteine (NAC) on the injury of putative parvalbumin positive interneurons defined by molecular marker and hippocampal long-term potentiation (LTP), a marker of neural plasticity following acute carbon monoxide (CO) poisoning. Methods: Adult Sprague-Dawley rats were exposed to 1100 ppm CO for 40 minutes followed by 3000 ppm CO for 20 minutes. Animals received daily intraperitoneal injection of NAC (150 mg/kg) for 5 days after CO exposure. Changes in learning and spatial memory were evaluated by Y-maze test 5 days after the poisoning. In vivo LTP in hippocampal CA1 area was evaluated by using extracellular electrophysiological technique. Immunohistochemical staining were adopted to observe expressional damages of parvalbumin (PV) immunoreactive interneurons in the hippocampus following the poisoning. Results: Acute CO intoxication resulted in no changes in memory performance at Y-maze test but a significant reduction of LTP in the in hippocampal CA1 area. There was also a significant reduction of PV (+) interneurons in the hippocampal CA1 area 5 days after CO poisoning. Daily treatment of NAC significantly improved hippocampal LTP impairment and reduced immunoreactivity for PV in the hippocampus following the acute CO poisoning. Conclusion: The results of this study suggest that reduction of hippocampal LTP and PV (+) interneurons in the hippocampus is sensitive indicator for brain injury and daily NAC injections can be the alternative therapeutics for the injury induced by acute CO poisoning.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.337-343
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• 2010

Long-term potentiation (LTP) and long-term depression (LTD) have both been studied as mechanisms of ocular dominance plasticity in the rat visual cortex. In a previous study, we suggested that a developmental increase in serotonin [5-hydroxytryptamine (5-HT)] might be involved in the decline of LTP, since 5-HT inhibited its induction. In the present study, to further understand the role of 5-HT in a developmental decrease in plasticity, we investigated the effect of 5-HT on the induction of LTD in the pathway from layer 4 to layer 2/3. LTD was inhibited by 5-HT ($10{\mu}M$) in 5-week-old rats. The inhibitory effect was mediated by activation of 5-$HT_2$ receptors. Since 5-HT also regulates the development of visual cortical circuits, we also investigated the role of 5-HT on the development of inhibition. The development of inhibition was retarded by chronic (2 weeks) depletion of endogenous 5-HT in 5-week-old rats, in which LTD was reinstated. These results suggest that 5-HT regulates the induction of LTD directly via activation of 5-$HT_2$ receptors and indirectly by regulating cortical development. Thus, the present study provides significant insight into the roles of 5-HT on the development of visual cortical circuits and on the age-dependent decline of long-term synaptic plasticity.

• Annals of Clinical Neurophysiology
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• 제13권1호
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• pp.1-12
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• 2011

Transcranial magnetic stimulation (TMS) is a non-invasive tool used to study aspects of human brain physiology, including motor function and the pathophysiology of various brain disorders. A brief electric current passed through a magnetic coil produces a high-intensity magnetic field, which can excite or inhibit the cerebral cortex. Although various brain regions can be evaluated by TMS, most studies have focused on the motor cortex where motor evoked potentials (MEPs) are produced. Single-pulse and paired-pulse TMS can be used to measure the excitability of the motor cortex via various parameters, while repetitive TMS induces cortical plasticity via long-term potentiation or long-term depression-like mechanisms. Therefore, TMS is useful in the evaluation of physiological mechanisms of various neurological diseases, including movement disorders and epilepsy. In addition, it has diagnostic utility in spinal cord diseases, amyotrophic lateral sclerosis and demyelinating diseases. The therapeutic effects of repetitive TMS on stroke, Parkinson disease and focal hand dystonia are limited since the duration and clinical benefits seem to be temporary. New TMS techniques, which may improve clinical utility, are being developed to enhance clinical utilities in various neurological diseases.

• 생물정신의학
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• 제6권2호
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• pp.149-152
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• 1999

Transgenic mice models of Alzheimer's disease were produced by overexpressing APP(amyloid precursor protein) mutant and presenilin mutant genes using the promotors that induced neuronal expression. The neuropathologies, electrophysiological changes and behavioral changes that were demonstrated in these transgenic mice models were amyloid changes, gliotic changes, A-beta increases, deficit in LTP(long-term potentiation) and behavioral changes. Some or all of the above changes were found in each transgenic mice model. These models generally showed amyloid neuropathology but they usually lacked the neurofibrillary tangles. So, they can be regarded as partial models of Alzheimer's disease. The development of them is undoubtedly the great progress toward future research.

• The Korean Journal of Physiology and Pharmacology
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• 제6권2호
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• pp.113-119
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• 2002

Long-term potentiation (LTP) at hippocampal CA3-CA1 synapses is often associated with increases in quantal size, traditionally attributed to enhanced availability or efficacy of postsynaptic glutamate receptors. However, augmented quantal size might also reflect increases in neurotransmitter concentration within the synaptic cleft since AMPA-type glutamate receptors are not generally saturated during basal transmission. Here we report evidence that peak cleft glutamate concentration $([glu]_{cleft})$ increases during LTP, as indicated by a lessening of the blocking effects of rapidly unbinding antagonists of AMPA. The efficacy of slowly equilibrating antagonists remained unchanged. The elevated $[glu]_{cleft}$ helps support the increased quantal amplitude of AMPA-type EPSCs (excitatory postsynaptic currents) during LTP.

• Molecules and Cells
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• 제28권6호
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• pp.501-507
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• 2009

Fragile X syndrome (FXS) is caused by a lack of the fragile X mental retardation protein (FMRP) due to silencing of the Fmr1 gene. As an RNA binding protein, FMRP is thought to contribute to synaptic plasticity by regulating plasticity-related protein synthesis and other signaling pathways. Previous studies have mostly focused on the roles of FMRP within the hippocampus - a key structure for spatial memory. However, recent studies indicate that FMRP may have a more general contribution to brain functions, including synaptic plasticity and modulation within the prefrontal cortex. In this brief review, we will focus on recent studies reported in the prefrontal cortex, including the anterior cingulate cortex (ACC). We hypothesize that alterations in ACC-related plasticity and synaptic modulation may contribute to various forms of cognitive deficits associated with FXS.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 제3회 추계심포지움
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• pp.125-132
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• 1995

In neurons, nitric oxide(NO) is produced by neuronal nitric oxide synthase following stimulation of N-methyl-D-aspartate(NMDA) receptors and the subsequent influx of Ca$\^$2+/. NO, induced in this manner, reportedly plays critical roles in neuronal plasticity, including neurite outgrowth, synaptic transmission, and long-term potentiation(LTP) (1-7). However, excessive activation of NMDA receptors has also been shown to be associated with various neurological disorders, including focal ischemia, epilepsy, trauma, neuropathic pain and chronic neurodegenerative maladies, such as Parkinson's disease, Hungtington's disease and amyotrophic lateral sclerosis(8). The paradox that nitric oxide(NO) has both neuroprotective and neurodestructive effects may be explained, at least in part, by the finding that NO effects on neurons are dependent on the redox state. This claim may be supported by the recent finding that tissue concentrations of cysteine approach 700 ${\mu}$M in settings of cerebral ischemia (9), levels of thiol that is expected to influence both the redox state of the system and the NO group itself(10).

• 대한불안의학회지
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• 제6권2호
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• pp.102-108
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• 2010

Objective : Although studies have explored responses to fear had been assessed using various psychophysiological methods, results have been inconsistent. The present study examined psychophysiological responses in healthy subjects after viewing fear stimuli in a video clip for set up future fear related psychophysiological studies. Methods : We monitored three psychophysiological variables (electroencephalography, skin temperature, and heart rate variability) in adults who watched either a control stimulus movie clip or a fear-inducing movie clip. Results : In 16 healthy adults, theta activity decreased significantly after the fear stimulus as compared to the normal stimulus. However the participants showed no differences in heart rate variability or skin temperature between the fear and normal control stimulus situations. Conclusion : In the limbic area, theta activity corresponds with information processing, integration into previous memories and long-term potentiation. In this study, we suggest decreased theta activity represents amygdalo-hippocampal activity, associated with fear, short-term memory, and memory extinction in the healthy adults. Further studies are needed to evaluate the interaction of fear, memory, and the pathophysiology of anxiety disorder in patient with anxiety disorders.

• 수면정신생리
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• 제3권1호
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• pp.15-24
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• 1996

REM 수면이 학습 및 기억 과정에 관련이 있다는 증거는 많으나 아직도 향후 밝혀져야 할 부분이 많다. 학습후에는 REM 수면이 유의하게 증가한다는 주장과 증가하지 않는다는 연구결과가 있어 의견의 일치를 보이지 않고 있다. 그러나 연구 결과들을 종합하면 내용이 쉽고 단순한 학습후에는 REM 수면의 증가가 없으나 내용이 복잡하고 생소하며 정서적으로 중요한 학습후에는 유의한 REM 수면의 증가를 보인다는 점에서는 일치하고 있다. 이 결과는 Rotenberg(6)의 학습에 대한 두가지의 서로 상반된 행동양식, 즉 탐색활동과 탐색의 포기라는 관점에서의 해석과 일치한다. 아무튼 REM 수면은 장기 기억의 고정과 유지에 중요하며, 불완전한 학습은 REM 수면의 증가를 자극하는 일련의 사건들은 가동시키고 이는 학습을 완성하는데 기여하는 것으로 보인다. 학습전, 후의 REM 수면의 박탈에 대한 연구도 REM 수면이 학습/기억 과정과 밀접히 관련됨을 시사한다. 학습전 REM 수면의 박탈에 대한 연구는 REM 수면이 장기기억에서 저장의 고정과정에 적극적으로 관여됨을 시사한다. 학습후 REM 수면의 박탈에 대한 연구는 REM 수면 "window"라는 개념을 이끌어 냈고 "window"에 해당하는 시간에 REM 수면을 박탈하면 학습장애를 초래하는데, 특히 학습 후 첫번째 나타나는 REM 수면 "window"가 학습과정에서 가장 중요함을 시사한다. REM 수면의 발생과 관련된 뇌의 전기신경생화학적인 일련의 사건들이 기억과 관련된다는 증거들이 많다. REM 수면중 발생하는 해마의 리듬과 기억의 신경생물 학적 기전에 관한 모델중 대표적인 모델인 장기증폭(long-term potentiation)의 관련성이 제안되고 있으며 REM 수면의 박탈은 중추신경계에서 단백질 합성의 장애 및 acetylcholine과 catecholamine 등의 신경 전달물질의 활성에 장애를 주고 이는 기억장애의 결과로 나타난다는 연구들이 있다. 아직도 REM 수면의 기억관련 기능은 의문점이 많다. 향후 분자생물학의 응용 및 뇌의 대사활동이 수면주기에 따라 아주 다름을 보여주는 brain metabolic mapping technique의 이용은 단백질의 합성의 수준에서 REM 수면과 기억/학습과정의 관련성에 대한 이해를 높여줄 것이다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 1998년도 Advances in Ginseng Research - Proceedings of the 7th International Symposium on Ginseng -
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• pp.1-11
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• 1998

Ameliorating mechanisms of red ginseng on learning deficits were investigated in the following 3 experiments; its effects on 1) place learning deficits in aged rats and in young rats with selective hippocampal lesions (behavioral study), 2) long-term potentiation in the hippocampal formation (neuro- physiological study), and 3) ChAT (choline acetyl transferase) activity in various brain regions of aged rats (pharmacological study). In the behavioral study, first, performance in the place learning tasks were compared among 3 groups of young and aged rats; control young intact rats (10-12 week old) treated with water, aged rats (28-32 month old) treated with water, and aged rats (28-32 month old) treated with red ginseng (100 mghglday) suspended in water. Second, performance in the place learning tasks was compared among 3 groups of young rats; control intact rats treated with water, rats with bilateral hippocampal lesions treated with water, and rats with bilateral hippocampal lesions treated with red ginseng (100 mg/kg/day). Each rat in these 2 behavioral experiments was tested with the 3 types of the place learning tasks in a circular open field using intracranial self-stimulation (ICSS) as reward. The ICSS reward was delivered if the rat (1) moved distance of 100-160 cm (DMT): (2) entered an experiment-determined reward place within the open field, and this place was randomly varied in sequential trials (RRPST); or (3) entered 2 specific places, and did a shuttle behavior between the 2 places (PLT). Performance of the aged rats in the ginseng group was not significantly different from that of control young rats in ICSS (current intensity, bar press rates), DMT and RRPST. However, treatment with red ginseng significantly ameliorated place-navigation learning deficits in aged rats in the PLT. Similarly, red ginseng ameliorated learning and memory deficits in young rats with hippocampal lesions in the same tasks. In the neurophysiological study using young rats, perfusion of hippocampal slices with non-sapon in fraction of red ginseng significantly enhanced magnitudes of the long-term potentiation (LfP) in the CA3 subfield. In the pharmacological study, treatment with red ginseng did not affect ChAT activity in aged rat brain including the hippocampal formation. These results strongly suggest that red ginseng ameliorates learning and memory deficits in aged rats through actions on the CA3 subfield of the hippocampal formation, which were independent of the presynaptic components of the cholinergic system