• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.80-80
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• 2003

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by marked cell death in the striatum and cortex. Stereotaxic injection of quinolinic acid (QA) into striatum results in a degeneration of GABAergic neurons and exhibits abnormal motor behaviors typical of the illness. The objective of this study was carried out to obtain basic information about whether parthenogenetic mouse embryonic stem (PmES) cells are suitable for cell replacement therapy of HD. To establish PmES cell lines, hybrid F1 (C57BL/6xCBA/N) mouse oocytes were treated with 7% ethanol for 5 min and cytochalasin-B for 4 hr to initiate spontaneous cleavage. Thus established PmES cells were induced to differentiate using bFGF (20ng/ml) followed by selection of neuronal precursor cells for 8 days in N2 medium. After selection, cells were expanded at the presence of bFGF (20 ng/ml) for another 6 days, then a final differentiation step in N2 medium for 7 days. To establish recipient animal models of HD, young adult mice (7 weeks age ICR mice) were lesioned unilaterally with a stereotaxic injection of QA (60 nM) into the striatum and the rotational behavior of the animals was tested using apomorphine (0.1mg/kg, IP) 7 days after the induction of lesion. Animals rotating more than 120 turns per hour were selected and the differentiated PmES cells (1$\times$10$^4$cells/ul) were implanted into striatum. Four weeks after the graft, immunohistochemical studies revealed the presence of cells reactive to anti-NeuN antibody. However, only a slight improvement of motor behavior was observed. By Nissl staining, cell mass resembling tumor was found at the graft site and near cortex which may explain the slight behavioral improvement. Detailed experiment on cell viability, differentiation and migration explanted in vivo is currently being studied.

• Korean Journal of Clinical Laboratory Science
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• v.47 no.1
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• pp.46-50
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• 2015

The previous studies showed that the visual imagery activated the occipital and posterior inferior temporal area of the brain, and the damage to the occipital cortex impaired the visual mental imagery. We studied current-source distribution of electroencephalography (EEG) to observe neuronal activity during imagery tennis playing. Eleven healthy volunteers were enrolled. All volunteers were right-handed males and novices for tennis playing. The mean age of them was 24.9 years. The EEGs were recorded on the scalp electrodes located according to the International 10~20 System. The number of electrodes was 25 channels including subtemporal electrodes. The EEG recording session was 13 min including 5 segments: resting-I, scenery-slide show, resting-II, watching tennis-game video, and imagery-tennis playing. The recoding durations were 3, 2, 3, 2, and 3 min respectively. Five 'artifact free 3-sec segments' were selected in each segment of 'imagery-tennis playing' and 'resting-II'. We did the frequency domain analysis with the EEG segments using a distributed model of current-source analysis. The statistical-nonparametric maps (SnPMs) were obtained between the segments of 'imagery-tennis playing' and the segments of 'resting-II' (p<0.01). The significant change of current-source density was observed only in alpha-2 frequency band (10~12 Hz). The current-sourcedensity was increased in the hippocampus, parahippocampus, and occipital fusiform gyrus in the right cerebral hemisphere (p<0.01). Imaginary-tennis playing may activate the hippocampal-occipital alpha networks of nondominant hemisphere.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.3
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• pp.279-286
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• 2016

Caffeic acid phenethyl ester (CAPE), derived from honeybee hives, is a bioactive compound with strong antioxidant activity. This study was designed to test the neuroprotective effect of CAPE in 3-nitropropionic acid (3NP)-induced striatal neurotoxicity, a chemical model of Huntington's disease (HD). Initially, to test CAPE's antioxidant activity, a 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) antioxidant assay was employed, and CAPE showed a strong direct radical-scavenging effect. In addition, CAPE provided protection from 3NP-induced neuronal cell death in cultured striatal neurons. Based on these observations, the in vivo therapeutic potential of CAPE in 3NP-induced HD was tested. For this purpose, male C57BL/6 mice were repeatedly given 3NP to induce HD-like pathogenesis, and 30 mg/kg of CAPE or vehicle (5% dimethyl sulfoxide and 95% peanut oil) was administered daily. CAPE did not cause changes in body weight, but it reduced mortality by 29%. In addition, compared to the vehicle-treated group, robustly reduced striatal damage was observed in the CAPE-treated animals, and the 3NP-induced behavioral deficits on the rotarod test were significantly rescued after the CAPE treatment. Furthermore, immunohistochemical data showed that immunoreactivity to glial fibrillary acidic protein (GFAP) and CD45, markers for astrocyte and microglia activation, respectively, were strikingly reduced. Combined, these data unequivocally indicate that CAPE has a strong antioxidant effect and can be used as a potential therapeutic agent against HD.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.4
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• pp.207-214
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• 2002

The present study was designed to clarify whether tacrine affects the release of catecholamines (CA) from the isolated perfused model of rat adrenal gland or not and to elucidate the mechanism of its action. Tacrine $(3{\times}10^{-5}{\sim}3{\times}10^{-4}\;M)$ perfused into an adrenal vein for 60 min inhibited CA secretory responses evoked by ACh $(5.32{\times}10^{-3}\;M),$ DMPP (a selective neuronal nicotinic agonist, $10^{-4}$ M for 2 min) and McN-A-343 (a selective muscarinic M1-agonist, $10^{-4}$ M for 2 min) in relatively dose- and time- dependent manners. However, tacrine failed to affect CA secretion by high $K^+\;(5.6{\times}10^{-2}\;M).$ Tacrine itself at concentrations used in the present experiments did not also affect spontaneous CA output. Furthermore, in the presence of tacrine $(10^{-4}\;M),$ CA secretory responses evoked by Bay-K-8644 (an activator of L-type $Ca^{2+}$ channels, $10^{-4}\;M),$ but not by cyclopiazonic acid (an inhibitor of cytoplasmic $Ca^{2+}-ATPase,\;10^{-4}\;M),$ was relatively time-dependently attenuated. Also, physostigmine $10^{-4}\;M),$ given into the adrenal gland for 60 min, depressed CA secretory responses evoked by ACh, McN-A-343 and DMPP while did not affect that evoked by high $K^+.$ Collectively, these results obtained from the present study demonstrate that tacrine greatly inhibits CA secretion from the perfused rat adrenal gland evoked by stimulation of cholinergic (both nicotinic and muscarinic) receptors, but does fail to affect that by direct membrane-depolarization. It is suggested that this inhibitory effect of tacrine may be exerted by blocking both the calcium influx into the rat adrenal medullary chromaffin cells without $Ca^{2+}$ release from the cytoplasmic calcium store, that is relevant to the cholinergic blockade. Also, the mode of action between tacrine and physostigmine in rat adrenomedullary CA secretion seems to be similar.

• Journal of Korean Neurosurgical Society
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• v.57 no.5
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• pp.335-341
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• 2015

Objective : The main causes of spinal cord ischemia are a variety of vascular pathologies causing acute arterial occlusions. We investigated neuro-protective effects of kefir on spinal cord ischemia injury in rats. Methods : Rats were divided into three groups : 1) sham operated control rats; 2) spinal cord ischemia group fed on a standard diet without kefir pretreatment; and 3) spinal cord ischemia group fed on a standard diet plus kefir. Spinal cord ischemia was performed by the infrarenal aorta cross-clamping model. The spinal cord was removed after the procedure. The biochemical and histopathological changes were observed within the samples. Functional assessment was performed for neurological deficit scores. Results : The kefir group was compared with the ischemia group, a significant decrease in malondialdehyde levels was observed (p<0.05). Catalase and superoxide dismutase levels of the kefir group were significantly higher than ischemia group (p<0.05). In histopathological samples, the kefir group is compared with ischemia group, there was a significant decrease in numbers of dead and degenerated neurons (p<0.05). In immunohistochemical staining, hipoxia-inducible factor-$1{\alpha}$ and caspase 3 immunopositive neurons were significantly decreased in kefir group compared with ischemia group (p<0.05). The neurological deficit scores of kefir group were significantly higher than ischemia group at 24 h (p<0.05). Conclusion : Our study revealed that kefir pretreatment in spinal cord ischemia/reperfusion reduced oxidative stress and neuronal degeneration as a neuroprotective agent. Ultrastructural studies are required in order for kefir to be developed as a promising therapeutic agent to be utilized for human spinal cord ischemia in the future.

• Journal of Oriental Neuropsychiatry
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• v.21 no.2
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• pp.61-73
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• 2010

Objectives : The purpose of this study was to assess anti-depressive effects of Bee Venom(BV) on an Animal Model of Depression induced immobility stress. Methods : There was 2 pre-experiments MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and Western blot test and 3 main experiments ; forced swimming test, tail suspension test and Y-maze task. Male rats were used for main experiment. The subject was divided into 4 groups(1. control group injected only saline, without immobility stress 2. Negative group injected saline after 2 hours immobility stress 3. Positive group injected Amitriptyline after 2 hours immobility stress 4. BV group injected Bee Venom after 2 hours immobility stress). Each group consisted of 6 rats. Forced swimming test, tail suspension test, Y-maze task were used to evaluate anti-depressive effect of Bee Venom. Results : In MTT assay, as the density of BV increased, the existence rate of primary neuronal cell increased. In Western blot test, the density of CREB and AKT was increasing as time went by. In forced swimming test, BV group showed immobility decreased more than Normal group and Positive group. In tail suspension test, Normal group and Positive group showed immobility decreased more than BV group. In Y-maze task, BV group showed immobility decreased more than Normal group, but Positive group showed immobility decreased more than BV group. Conclusions : These results suggest that Bee Venom may have anti-depressive effect on depression.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.85-85
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• 2001

Sam-Hwang-Sa-Shim-Tang(SHSST), a traditional Chinese medicine, composed of Rhei rhizoma, Scutellaria radix, and Coptidis rhizoma were used in the several disease including hypertension, constipation, and hemorrhage. In the present study, we investigated the neuroprotective effects of SHSST and its ingredients on the ischemia/ reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 120 min and reperfusion was continued for 22 h. SHSST (450 mg/kg), Rhei rhii oma (100 mg/kg), Coptidis rhizoma (100 mg/kg), and Scutellaria radik (100 mg/kg) were orally administered twice, promptly prior to reperfusion and 2 h after the repefusion. Total infarction volume in the ipsilateral hemisphere of ischemia/ reperfusion rats was significantly lowed by the treatments of SHSST (39.2%) and Scutellaria radix (66.5%). However, Coptidis rhizoma did not show any significant effects on the total infarct volume. The inhibiting effect of Scutellaria radix on the total infarct volume was more potent than that of SHSST. In addition, Scutellaria radix significantly inhibited myeloperoxidase (MPO) activity, an index of neutrophil infiltration in ischemic brain tissue. However, there was marked mismatch between total infarct volume and MPO activity in the Scutellaria radix-treated rats. Our findings suggest that Scutellaria radix as an ingredient of SHSST plays a protective role in ischemia-induced brain injury by inhibiting neutrophil infiltration. The effects of Rhei rhizoma on transient brain ischemia-induced neuronal injury are under study.

• Korean Journal of Pharmacognosy
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• v.39 no.3
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• pp.213-217
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• 2008

Oxidative stress is considered to play an important role in a variety of neurodegenerative disorders of central nervous system. The immortalized mouse hippocampal cell line, HT22, phenotypically resembles neuronal precursor cells but lacks functional ionotropic glutamate receptors, thus excluding excitotoxicity as a cause for glutamate triggered cell death. Therefore, HT22 cells are a useful model for studying oxidative glutamate toxicity. In this study, we examined whether the methanol extracts of some native plants at Mt. Baekdu could protect HT22-immortalized hippocampal cells against glutamate-induced oxidative stress. Seventy-eight plants sources were collected at Mt. Baekdu, and extracted with methanol. These extracts had been screened the protective effects against glutamate-induced oxidative damage in HT22 cells at the 100 and 300 ${\mu}g/ml$. Of these, thirteen methanolic extracts, Acer mono (leaf), Artemisia stolonifera (aerial part), Carduus crispus (aerial part), Carex mongolica (whole plant), Clematis hexapetala (whole plant), Galeopsis bifida (aerial part), Galium verum (whole plant), Ganoderma lucidum (whole plant), Ixeris chinensis (whole plant), Malva verticillata (aerial part), Polygonum senticosum (whole plant), Rebes mandshricum (branch), and Taraxacum mongolicum (aerial part), showed significant protective effects against glutamate-induced oxidative damage in HT22 cells.

• Journal of Korean Biological Nursing Science
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• v.10 no.2
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• pp.176-183
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• 2008

Purpose: The purpose of this study was to identify the effect of Environmental Enrichment (EE) on improvement of motor function in animal models of Parkinson's Disease. Methods: Male C57BL6 mice weighing 25-30 g, at the age of 12 wks were used in this study. The animals were injected MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin, 20 mg/kg in saline, i.p.) 4 times a day at every 2 hr, and raised in EE cage for 14 days. On day 14, after behavior test, all mice were sacrificed for immunohistochemistry. All values were expressed as means$\pm$S.E.M. Statistical significance was evaluated using a one way ANOVA followed by Sheffe test. Results: There was a significant difference between the experimental group and the control group in the behavior test. Also EE significantly reduced of TH positive cell loss in Substantia nigra pars compacta as compared to the result of MPTP treatment. Conclusion: Based on these findings, it is reasonable to assume that the environmental enrichment prevents dopaminergic neuronal loss and improves disarrangement of motor function and behavioral disability induced by MPTP.

• Journal of Korean Neurosurgical Society
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• v.54 no.1
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• pp.8-13
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• 2013

Objective : This study investigates the effect of valproic acid (VPA) on expression of neural stem/progenitor cells (NSPCs) in a rat spinal cord injury (SCI) model. Methods : Adult male rats (n=24) were randomly and blindly allocated into three groups. Laminectomy at T9 was performed in all three groups. In group 1 (sham), only laminectomy was performed. In group 2 (SCI-VPA), the animals received a dose of 200 mg/kg of VPA. In group 3 (SCI-saline), animals received 1.0 mL of the saline vehicle solution. A modified aneurysm clip with a closing force of 30 grams was applied extradurally around the spinal cord at T9, and then rapidly released with cord compression persisting for 2 minutes. The rats were sacrificed and the spinal cord were collected one week after SCI. Immunohistochemistry (IHC) and western blotting sample were obtained from 5 mm rostral region to the lesion and prepared. We analyzed the nestin immunoreactivity from the white matter of ventral cord and the ependyma of central canal. Nestin and SOX2 were used for markers for NSPCs and analyzed by IHC and western blotting, respectively. Results : Nestin and SOX2 were expressed significantly in the SCI groups but not in the sham group. Comparing SCI groups, nestin and SOX2 expression were much stronger in SCI-VPA group than in SCI-saline group. Conclusion : Nestin and SOX2 as markers for NSPCs showed increased expression in SCI-VPA group in comparison with SCI-saline group. This result suggests VPA increases expression of spinal NSPCs in SCI.