• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.151-158
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• 1996

Following the subcutaneous administration of $R(-)N^6-(2-phenylisopropyl)adenosine(600\;nmol/kg/hr)$ to rats for 1 week using t$Alzet^{\circledR}$ mini-osmotic pumps, $A_1$ adenosine receptor functions were determined using $[^3H]DPCPX$ binding, $[^{35}S]GTP_{\gamma}S$ binding, and adenylyl cyclase assays. $A_1$ adenosine receptor binding and the inhibition of adenylyl cyclase activity by PIA was not altered in cerebrocortical membranes prepared from PIA-treated rats. However, there was a significant decrease in the $A_1$ adenosine receptor-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ binding to cerebrocortical membranes prepared from PIA-treated rats(22.0% decrease in basal activity; 19.7% decrease in maximal activity). These results suggest that the desensitization of $A_1$ adenosine receptors following chronic administration involves agonist-induced uncoupling of the receptors from G proteins rather than alteration of $A_1$ adenosine receptor molecules. It is also suggested that the determination of stimulation of $[^{35}S]GTP_{\gamma}S$ binding to G proteins is a suitable tool in studying the receptor regulation including desensitization

• Journal of Pharmacopuncture
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• v.20 no.1
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• pp.10-17
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• 2017

Objectives: Boswellic acid (BA), a compound isolated from the gum-resin of Boswellia carterii, is a pentacyclic terpenoid that is active against many inflammatory diseases, including cancer, arthritis, chronic colitis, ulcerative colitis, Crohn's disease, and memory impairment, but the mechanism is poorly understood. This study investigated the effects of boswellic acid on spatial learning and memory impairment induced by trimethyltin (TMT) in Wistar rats. Methods: Forty male Wistar rats were randomly divided into 5 groups: Normal group, TMT-administrated rats (8.0 mg/kg, Intraperitoneally, i.p.) and TMT + BA (40, 80 and 160 mg/kg, i.p.)-administrated rats. BA was used daily for 21 days. To evaluate the cognitive improving of BA, we performed the Morris water maze test. Moreover, to investigate the neuroprotective effect of BA, we determined the acetylcholinesterase (AchE) activity, the malondialdehyde (MDA) level as a marker of lipid peroxidation, and the glutathione (GSH) content in the cerebral cortex. Results: Treatment with TMT impaired learning and memory, and treatment with BA at a dose of 160 mg/kg produced a significant improvement in learning and memory abilities in the water maze tasks. Consistent with behavioral data, the activity of AChE was significantly increased in the TMT-injected rats compared to the control group (P < 0.01) whereas all groups treated with BA presented a more significant inhibitory effect against AChE than the TMT-injected animals. In addition, TMT reduced the GSH content and increased the MDA level in the cerebral cortex as compared to the control group) P < 0.01). On the other hand, treatment with BA at 160 mg/kg slightly increased the GSH content and reduced the MDA level in comparison to the TMT-administered group (P < 0.01). Conclusion: The above results suggest that the effect of BA in improving the cognitive function may be mediated through its antioxidant activity.

• Molecules and Cells
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• v.20 no.2
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• pp.189-195
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• 2005

Ethanol has long been implicated in triggering apoptotic neurodegeneration. We examined the effects of ethanol on the rat brain during synaptogenesis when a spurt in brain growth occurs. This period corresponds to the first 2 postnatal weeks in rats and is very sensitive to ethanol exposure. Ethanol was administered subcutaneously to 7-day- postnatal rat pups by a dosing regimen of 3 g/kg at 0 h and again at 2 h. Blood ethanol levels peaked ($677{\pm}16.4mg/dl$) at 4 h after the first ethanol administration. The cerebral cortexes of the ethanol-treated group showed several typical symptoms of apoptosis such as chromosome condensation and disintegration of cell bodies. Activated caspase-3 positive cells were found in the cortex within 2 h of the first injection, and reached a peak at 12 h. In addition, TUNEL staining revealed DNA fragmentation in the same regions. These results demonstrate that acute ethanol administration causes neuronal cell death via a caspase-3-dependent pathway within 24 h, suggesting that activation of caspase-3 is a marker of the developmental neurotoxicity of ethanol.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.157-163
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• 1993

Intramolecular excimer formation with the fluorescent probe 1,3-di(1-pyrenyl)propane (Py-3-Py) was used to investigate the effects of methanol, ethanol, 1-propanol, 1-butanol, 1-pentanol, 1-hexanol, 1-heptanol, 1-octanol, 1-nonanol and 1-decanol on the lateral diffusion of synaptosomal plasma membrane vesicles isolated from bovine cerebral cortex (SPMV). The n-alkanols increased the excimer to monomer fluorescence intensity ratio (I'/I) of Py-3-Py in the SPMV. In a dose-dependent manner, n-alkanols increased lateral diffusion of hydrocarbon region of bulk (inner+outer monolayers) SPMV lipid bilayers, and the potencies of n-alkanols up to l-nonanol increased with carbon chain length. It appears that the potencies in bilayer fluidization due to the lateral diffusion increase by 1 order of magnitude as the carbon chain length increases by two carbon atoms. The cut-off phenomenon was reached at 1-decanol, where further increase in hydrocarbon length resulted in a decrease in pharmacological activity.

• Journal of Haehwa Medicine
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• v.26 no.1
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• pp.1-10
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• 2017

Objectives: The aim of this study is (1) to investigate the historic changes and pharmacological efficacies of Woohwangchungsim-won and (2) to discuss the necessities for Woohwangchungsim-won's clinical applications. Methods: This study was performed through (1) investigating the ancient literature records related with Woohwangchungsim-won and analyzing Woohwangchungsim-won's composition, dosage and indications, (2) searching articles about Woohwangchungsim-won on 10 major Korean web and 3 major foreign web article search engines and analyzing Woohwangchungsim-won's pharmacological efficacies and indications. Results: Woohwangchungsim-wom has been used for cerebrovascular diseases such as stroke and palpitation. Also, there are some ancient literature records of Woohwangchungsim-won's clinical applications in neuropsychiatric disorders such as depression and bipolar disorder. In addition, there have been a number of experimental studies which demonstrate Woohwangchungsim-won's neuroprotective effect on cerebral cortex and hippocampus injury. So, it is possible to infer that Woohwangchungsim-won can be used for the treatments of neuropsychiatric disorders associated with neuronal cell death in cerebral cortex and hippocampus. But there have been no or less experimental studies which demonstrate the pharmacological efficacy of Woohwangchungsim-won on such disease. Conclusion: It is necessary that further experimental studies which demonstrate Woohwangchungsim-won's pharmacological efficacy on neuropsychiatric disorders should be done and Woohwangchungsim-won's clinical applications should be expanded on the basis of those related experimental results.

• Korean Journal of Veterinary Research
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• v.11 no.1
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• pp.59-63
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• 1971

Current interest in ${\gamma}$-aminobutyric acid (GABA) has arisen from the convergence of several independent line of investigation leading to the demonstration that this and related substances are normal products of brain metabolism and that GABA has an important physiological action upon brain function as well as upon certain peripheral nervous structures. The interest for neurophysiologists has been enhanced by the importance of the discovery for the role of humoral mediator of synaptic transmission or regulator of neuronal activity in the central nervous system, particularly if it may shed some elight upon the nature of central inhibitory processes. In accordance with such an interest and importance, this work was performed in order to standardize the normal content as a preliminary investigation of so-called night active and daytime active animals GABA content in their brains when they are exposed to light and darkness. The method, through which the estimation has made in this work, was paper chromatographic method developed by Maynert and Klingman for the estimation of GABA content in animal tissues. The results obtained are summerized as follows: 1) GABA content in the cerebral cortex of house rat ranged from 90 to $310{\mu}g/gm$ of wet weight. 2) The content of GAGA ranging from 130 to $510{\mu}g/gm$ of wet weight was occurred from midbrain of the rat. 3) GABA content was ranged from 30 to $150 {\mu}g/gm$ of wet weight of the rat cerebellum. 4) The contents of fowl cerebral cortex, midbrain, and cerebellum are estimated as ranging 230-590, 250-620, $50-280{\mu}g/gm$ of wet weight, respectively. As a result, it may be concluded that among three brain tissues of both animals the midbrain is the highest region in GABA content. Fowl brain, on the other side, contains more higher GABA content than the house rat brain does.

• Journal of The Korean Society of Integrative Medicine
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• v.7 no.3
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• pp.171-180
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• 2019

Purpose : The purpose of this study was to investigate the difference in motor cortical excitability during mental practice and action observation in subjects with forward head posture. Methods : This study was performed in two groups, a forward head posture group (n=17) and a normal posture group (n=17). Electroencephalography (EEG) was conducted to investigate cerebral cortex activity, and six electrodes were attached to Fp1, Fp2, C1, C2, C3, and C4 to measure the relative alpha power, relative beta power, relative gamma power, and mu rhythms. The subjects were requested to perform the four different conditions, which were eye opening, eye closing, mental practice, and action observation for 300 seconds. Results : The results showed that the relative alpha waves showed a significant difference between the normal and forward head posture groups in the C1, C2, C3, and C4 regions with the eyes open (p<.05). The relative beta waves also showed a significant difference between the two groups in the Fp1 and Fp2 regions during action observation (p<.05). The relative gamma waves were significantly different between the normal and forward head posture groups in the Fp1 and Fp2 regions during action observation (p<.05) in C1, C2, and C3 with eyes closed (p<.05) and in C1, C2, C3, and C4 with eyes open (p<.05). Conclusion : The results of this study showed that EEG change in the forward head posture group was different from that in the normal control group in action observation rather than in mental practice. Therefore, we are expected to provide a neurophysiological basis for applying action observation to motor skill learning during exercise for correcting forward head posture.

• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.677-685
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• 2006

Purpose : This study aimed to investigate whether exogenous thyroxine($T_4$) treatment to alcohol-fed dams would ameliorate the detrimental effects of alcohol on the postnatal development of neuropeptide-Y(NPY)-containing neurons of the cerebral cortex and hippocampus of the offspring. Methods : Time-pregnant rats were divided into three groups. An alcohol-fed group A received 35 calories of liquid alcohol diet daily from gestation day 6; control group B was fed a liquid diet in which dextrin replaced alcohol isocalorically; and alcohol＋$T_4$ group C received 35 calories of liquid alcohol diet and exogenous thyroxine subcutaneously. The features of the growth and maturation of rat brain tissue were observed at 0, 7, 14, 21 and 28 postnatal days via immunohistochemistry. Results : Group C showed prominent NPY immunoreactivity in the cerebral cortex compared to group A and B at P7. In group C, NPY-containing neurons were widely distributed in the all layers of cerebral cortex after P14. Also, numerical decreases of NPY-containing neuron were not found according to increasing age in group C. A decrease of NPY-containing neurons, however, was clearly observed in group A compared to group C at P28. In the hippocampus, similar patterns appeared in groups B and C after P7. Especially, in groups B and C, NPY-containing fibers formed plexus in the cerebral cortex and hippocampus at P14. Conclusion : These results suggest that the increase of NPY synthesis caused by maternal administration of exogenous thyroxine may convalesce fetal alcohol effects, one of the effects of the dysthyroid state following maternal alcohol abuse.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.23-29
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• 1996

According to the traditional receptor model, competitive antagonists share with agonists the ability to bind to a common site on receptors, but they are different from agonist in that they cannot trigger the biological response-i.e., they lack intrinsic efficacy. Recent findings extend the model by indicating that not all antagonists display an intrinsic efficacy of zero but that some display 'inverse agonism'. In the present study we studied the inverse agonism at $A_1$ adenosine receptors in membranes prepared from rat cerebral cortex. Eight commercially available $A_1$ adenosine receptor antagonists (CGS-15943, ADPX, CPT, DPCPX, DPX, N-0840, PACPX and 8-PT) were screened for inverse agonism by measuring the extent of $[^{35}S]guanosine-5'-({\gamma}-thio)$ triphosphate $([^{35}S]GTP_{\gamma}S)$ binding to G proteins. The agonist-induced stimulation of $[^{35}S]GTP_{\gamma}S$ bindings was completely blocked in the presence of $A_1$ adenosine receptor antagonists. Under optimal conditions, two types of antagonists could be distinguished. Seven antagonists including DPCPX decreased the basal $[^{35}S]GTP_{\gamma}S$ binding in the absence of agonist, displaying inverse agonist activity. One (CGS-15943) had no effect on the basal bindings. N-ethylmaleimide treatment reduced the basal bindings as well as agonist-mediated stimulation of $[^{35}S]GTP_{\gamma}S$ bindings, indicating that a substantial amount of this binding reflects an activated state of the C proteins. In good agreement with these findings, 0.1 mM GTP decreased the apparent affinity of the receptors for the agonist PIA, increased that for DPCPX, and had no effect on that for CGS-15943.

• The Korea Journal of Herbology
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• v.31 no.1
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• pp.7-15
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• 2016

Objectives : Polygalae Radix (POL) has an ameliorating effect on learning and memory impairment caused by cerebral hypoperfusion. In regard to POL's action mechanism, this study was carried out to investigate the effects of POL on oxidative damage and neuronal apoptosis induced by cerebral hypoperfusion in rats.Methods : The cerebral hypoperfusion was induced by permanent bilateral common carotid artery occlusion (pBCAO) in Sprague-Dawley rats. POL was administered orally once a day (130 mg/kg of water-extract) for 28 days starting at 4 weeks after the pBCAO. Superoxide dismutase (SOD) activities and malondialdehyde (MDA) levels in the brain tissue were measured using ELISA method. Expressions of 4-hydroxynonenal (4HNE) and 8-hydroxy-2'- deoxyguanosine (8-OHdG) were observed using immunohistochemistry. In addition, neuronal apoptosis was evaluated with Cresyl violet staining, TUNEL labeling, and immunohistochemistry against Bax and caspase-3.Results : POL treatment significantly increased SOD activities and significantly reduced MDA levels in the cerebral cortex. The up-regulations of 4HNE and 8-OHdG expression caused by pBCAO in the CA1 of hippocampus were significantly attenuated by POL treatment. POL treatment also restored the reduction of CA1 thickness and CA1 neurons caused by pBCAO and significantly attenuated the apoptotic markers including TUNEL-positive cells, Bax, and caspase-3 expression in the CA1 of hippocampus.Conclusions : The results show that POL attenuated the oxidative damage in brain tissue and neuronal apoptosis in the hippocampus caused by the cerebral hypoperfusion. It suggests that POL can be a beneficial medicinal herb to treat the brain diseases related to cerebral hypoperfusion.