• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.115-122
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• 2016

Sleep, which is an essential part of human life, is modulated by neurotransmitter systems, including gamma-aminobutyric acid (GABA) and dopamine signaling. However, the mechanisms that initiate and maintain sleep remain obscure. In this study, we investigated the relationship between melatonin (MT) and dopamine D2-like receptor signaling in pentobarbital-induced sleep and the intracellular mechanisms of sleep maintenance in the cerebral cortex. In mice, pentobarbital-induced sleep was augmented by intraperitoneal administration of 30 mg/kg MT. To investigate the relationship between MT and D2-like receptors, we administered quinpirole, a D2-like receptor agonist, to MT- and pentobarbital-treated mice. Quinpirole (1 mg/kg, i.p.) increased the duration of MT-augmented sleep in mice. In addition, locomotor activity analysis showed that neither MT nor quinpirole produced sedative effects when administered alone. In order to understand the mechanisms underlying quinpirole-augmented sleep, we measured protein levels of mitogen-activated protein kinases (MAPKs) and cortical protein kinases related to MT signaling. Treatment with quinpirole or MT activated extracellular-signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK, and protein kinase C (PKC) in the cerebral cortex, while protein kinase A (PKA) activation was not altered significantly. Taken together, our results show that quinpirole increases the duration of MT-augmented sleep through ERK1/2, p38 MAPK, and PKC signaling. These findings suggest that modulation of D2-like receptors might enhance the effect of MT on sleep.

• Journal of Oriental Neuropsychiatry
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• v.30 no.3
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• pp.221-235
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• 2019

Objectives: The purpose of this study was to confirm the anti-amnesic effects of Bunsimgieum (BSGE) through its favorable acetylcholine (ACh) and, acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT) mRNA expressions, and antioxidant effect on scopolamine (Sco)-induced memory impairment in C57BL/6 mice. Methods: Six groups, a total of 20 intact or 100 Sco-induced mice were used in this study, based on their body weight. Half of each group underwent passive avoidance tests and the measurement of hippocampus AChE activity, ACh content, and ChAT mRNA expression, The remaining half of each group underwent a Morris water-maze test and antioxidant defense system measurement as well. Results: Significant reductions in the step-through latency times from the passive avoidance test and reductions in the escape latency times from the Morris water-maze test were observed with increases of hippocampal AChE activities and, reductions in ACh contents and ChAT mRNA expression in hippocampus, as a result of Sco intraperitoneal treatment, in this study. Additionally, the increases in cerebral cortical MDA levels and, reductions in GSH contents, SOD activities, and CAT activities were demonstrated in the Sco control mice compared with the intact vehicle control mice, respectively. However, 28 days of consecutive oral pre-treatment of BSGE hot water extracts of 400, 200, and 100 mg/kg, respectively, markedly and dose-dependently inhibited Sco treatment-related amnesia. Conclusions: The results demonstrate that the oral administration of BSGE hot water extracts reduces Sco-induced memory impairment, through preserving ACh, related to ChAT mRNA expressions, causes AChE inhibition, and enhances the cerebral antioxidant defense system.

• Korean Journal of Biological Psychiatry
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• v.22 no.2
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• pp.87-94
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• 2015

Objectives The power spectral analysis of electroencephalogram has been widely used to reveal the pathophysiology of the alcoholic brain. However, the results were not consistent and the three dimensional study can be hardly found. The purpose of this study was to investigate characteristics of the three dimensional electroencephalographic (EEG) activity of alcohol dependent patients using standardized low resolution electromagnetic tomography (sLORETA). Methods The participants consisted of 30 alcohol dependent patients and 30 normal healthy controls. All the participants were males who had refrained from alcohol at least one month and were not taking any medications. Thirty two channel EEG data was collected in the resting state with eyes-closed condition during 30 seconds. The three dimensional data was compared between two groups using sLORETA for delta, theta, alpha, beta1, beta2, and beta3 frequency bands. Results sLORETA revealed significantly increased brain cortical activity in alpha, beta1, beta2, and beta3 bands each in alcohol dependent patients compared to normal controls. The voxels showing the maximum significance were in the left transverse temporal gyrus, left superior temporal gyrus, left anterior cingulate, and left fusiform gyrus in alpha, beta1, beta2, and beta3 bands respectively. Conclusions These results suggest that chronic alcohol intake may cause neurophysiological changes in cerebral activity. Therefore, the measuring of EEG can be helpful in understanding the pathophysiology of cognitive impairements in alcohol dependence.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.573-580
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• 1998

The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.

• 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.

• Korean Journal of Oriental Medicine
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• v.4 no.1 s.4
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• pp.99-114
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• 1998

The effect of herbal medicine on glutamate mediated neurotoxicity was studied in mouse neurons in primary culture. Immature cerebral cortex neurons (ED14) were maintained for up to 2 weeks in vitro, and we investigated the expression pattern of neuron differentiation and cytotoxicity of cell death, including LDH activity. Neuronal maturation initiated on day 7 and the susceptibility to glutamate-induced cell death was highly sensitive on Day 11 (Fig. 1). Thus, the exposure of the neurons to glutamate caused a dose$(0.1mM{\sim}1mM)$ and time$(4h{\sim}24h)$-dependent neurotoxicity(Fig. 4). Glutamate-induced neurodegeneration was prevented by Shipchondaebotang(SD), Yollyounggobondan(YG), Yugmijihwangwon(YJ) and the death of neurons exposed to glutamate was blocked by the NMDA receptor antagonist MK-801 (Fig. 5).

• Journal of Oriental Neuropsychiatry
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• v.21 no.1
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• pp.109-124
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• 2010

Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.6
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• pp.326-333
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• 2020

Nitrate-nitrite-nitric oxide (NO) pathway is a major alternative source of NO and is essential for NO - dependent physiological functions in body. Food supplements having nitrate/nitrite can improve metabolic syndromes including hypertension through antioxidant activity or vasodilation. The purpose of this study was to observe the effects of fermented garlic (F. garlic) having high concentration of NO2- on changes in blood flow and nitric oxide synthesis in the cerebral cortex of rodents. The generation of nitric oxide detected by a chemi-luminescence detector was higher in F. Garlic compared with NaNO2 solution under artificial gastric juice with pH 2.0. Ether F. garlic or NaNO2 diluted with artificial cerebrospinal fluid was directly applied into around the needle probe of laser Doppler flow meter that was located on epidural surface of the cortex. Direct application of F. garlic resulted in increase of cerebral blood flow detected by a laser Doppler flow meter with a dose-dependent manner. Compared with NaNO2 solution, F. garlic produced changes in cerebral blood flow at lower concentration of NO2-. Pretreatment of methylene blue, a guanylyl cyclase inhibitor prevented upregulation of cerebral blood flow by the treatment of F. garlic. In addition, the application of F. garlic with 250, 500ppm of NO2- caused significantly the production of NO in the cortical tissue but NaNO2 solution with 500ppm of NO2- did not. In summary, these results suggested that F. garlic with high content of NO2- induce increase in cerebral blood flow through nitric oxide-dependent signal pathway.

• The Korean Journal of Physiology
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• v.10 no.2
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• pp.39-45
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• 1976

This study was conducted to see whether the hippocampectomy exerted facilitatory influence upon gastric ulceration in animals, and if so, whether the effect of hippocampectomy could be suppressed by adrenalectomy. 107 male rats were divided into 5 groups: rats that had over 90% of their hippocampal tissue removed through an opening on each side of the cerebral cortex(hippocampal group, N=21), rats that received bilateral adrenalectomy(adrenal group, N=29), rats that received adrenalectomy as well as hippocampectomy(hippocampo-adrenal group, N=10), rats that received damage to each side of the cortex over the hippocampus(cortical control group, N=20), and rats that had solely their head skin incised(normal control group, N=27). All rats were kept without restraint or food deprivation until on the 25th day after surgery, the stomach of each rat was inflated with 7ml of physiological saline and then removed under deep anesthesia. The mucosal surface was sketched under dissecting microscope, and enlarged photographs$(4{\times})$ were taken. The percentage of animals developing gastric ulcer in each animal group was calculated, the number of ulcer in each stomach was counted, and the total area of ulceration per stomach was measured on the Photograph with the aid of superimposed graph paper and expressed as permillage of total area of the glandular mucosa. Results obtained were as follows: 1. The percentage of animals developing gastric ulcer was significantly larger in the hippocampal group than they were in the hippocampo-adrenal, the adrenal, the cortical, and the normal control groups. 2. The mean number of ulcer per stomach was significantly larger in the hippocampal group than they were in the adrenal, the cortical control, and the normal control groups, while no significant difference existed between the hippocampal and the hippocampo-adrenal groups. 3. Total area of ulcer per stomach was significantly larger in the hippocampal group than they were in the cortical control and the normal control groups, but no significant differ-ence existed among the hippocampal, the adrenal, and the hippocampo·adrenal groups. 4. All measured values of the adrenal group were not significantly different from those of the hippocampo-adrenal, the cortical control, and the normal control groups. It is inferred from the above results that the hippocampus exerts an inhibitory influence upon gastric ulceration and that the hippocampal influence is mediated only partly through suppression of pituitary·adrenal activity.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.4
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• pp.462-467
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• 2019

Many studies in recent decades have revealed that olfactory stimulation by perfume or malodor inhalation exerts various psychological and physiological effects on humans. The most recent studies have examined the electrophysiological response of olfactory stimulation on the activity of human cortical nerve cells. The purpose of this current study is to quantitatively analyze what changes occur in the alpha activity in healthy participants (N=12) on olfactory stimulation using two types of odors (acacia and butanol). Exposure to the odor of acacia perfume was associated with a significant increase (66.7%) in alpha activity when compared with that of the no-odor background EEG. Exposure to the odor of butanol was associated with a significant reduction (33.3% to 41.7%) in EEG alpha activity when compared with that of the no-odor control. The results of this study demonstrated the potential to alter the cerebral cortex activity by olfactory stimulation. The results also suggest that olfactory perception has stimulatory effects on the function of the nervous system. In other words, it could be concluded from this study that inhalation of olfactory stimulation affected brain wave activities and mood states. Further research is needed to completely understand and describe the electrophysiological effects of different odors on the central nervous system.