• Applied Microscopy
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• v.30 no.2
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• pp.193-204
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• 2000

Nowadays, mongolian gerbil is widely utilized in the research of brain and water deprivation because of congenitally incomplete Willis' circle, audiogenic seizure in low noise, and special cholesterol metabolism without water absorption for a long time. In this study, we intended to identify the time lapse changes in the general morphoogy and ultrastructure of the catecholaminergic neurons of mongolian gerbil brain in after long-term water deprivation. Fifteen mongolian gerbils were divided into 3 groups (5, 10, and 20-day water deprivation groups), each with 5 mongolian gerbils. Additional 5 mongolian gerbils which received water without limitation were used as a control. The brain sections were immunostained using tyrosine hysroxylase (TH), $ dopamine-\beta-hydroxylase$ (DBH), and phenylethanolamine-N-methyltrasferase (PMNT) antibodies. And immunoreactive cells were observed by electromicroscopy for the ultrastructural changes . The TH-immunoreactive (TH-IR) nerve cells were observed in the para- and peri-ventricular nucleus of the 3 rd ventricle in the hypothalamus and the substantia nigra. The number of TH-IR neurons in these areas was decreased from the 5th day of the water deprivation to the 10 th day and reincreased until 20 th day water deprivation. The shape and density of the dopamine-secreting cells identified by immunohistochemistry showed changes in the continuous water deprivation. Electron microscopy revealed a round nucleus in the neurons of control group but 5-day water deprivation group showed a dense and irregularly shaped nucleus. Also in the 5-day water-deprived group, mitochondria was decreased in number and junctins were disappered. Endoplasmic reticulum, Golgi complex did not show changes after water-deprivation. In this results, we can conclude that dopamine are involved in the water metabolism in mongolian gerbil, and mongolian gerbil could be used as an animal model for the researches of water deprivation.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.132-140
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• 2007

Parkinson's disease is a common neurodegenerative disorder that is mainly caused by dopaminergic neuron loss in the substantia nigra. Several radiopharmaceutics have been developed to evaluate the integrity of dopaminergic neuronal system. In vivo PET and SPECT imaging of presynaptic dopamine imaing are already applied to Parkinson's disease and other parkinsonism, and can demonstrate the dopaminergic dysfunction. This review summarized the use of the presynaptic dopaminergic imaging in PD as biomarkers in evaluation of disease progression as well as in diagnosis of PD.

• Toxicological Research
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• v.9 no.2
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• pp.217-224
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• 1993

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a well-known dopamine neuron-specific toxin. But the involvement of oxidative damage in the pathogenesis of MPTP-induced parkinsonism is still uncertain. In this study, by using 2',7',-dichlorofluorescin diacetate(DCFH-DA) that detects intracellular oxidative processes, the effect of MPTP on dichlorofluorescein fluorescence in dissociated cells from fetal rat mesencephalon in culture was investigated. At 7th day in culture, cells were loaded with DCFH-DA, and exposed to 1 mM MPTP or MPP+. MPTP induced dichlorofluorescein-fluorescence which was peaked at 3 min and mostly faded away 30 min after MPTP treatment.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.72-83
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• 2003

Objective : The goal of the present study was to investigate the protective effect of Gamiheechum-tang (Jiaweixiqian-tang; GHCT) on brain tissue damage from chemical or ischemic insults. Methods : Levels of cultured cortical neuron death caused by toxic chemicals were measured by LDH release assay. Neuroprotective effects of GHCT on brain tissues were examined in vivo by ischemic model of middle cerebral artery (MCA) occlusion. Results : Animal groups treated with GBCT showed significantly decreased hypertension, and reduced levels of aldosterone, dopamine, and epinephrine in the plasma. GHCT treatments ($l0-200\mu\textrm{g}/ml$) significantly decreased cultured cortical neuron death mediated by AMPA, kainate, BSO, or Fe2+ when measured by LDH release assay. Yet, cell death mediated by NMDA was effectively protected by GHCT at the highest concentration examined ($200\mu\textrm{g}/ml$). In the in vivo experiment examining brain damage by MCA occlusion, affected brain areas by ischemic damage and edema were significantly less in animal groups administered with GHCT compared to the non-treated control group. Neurological examinations of forelimbs and hindlimbs showed that GHCT treatment improved animals' recovery from ischemic injury. Moreover, the extent of injury in cortical and hippocampal pyramidal neurons in ischemic rats was much reduced by GHCT, whose morphological features were similarly observed in non-ischemic animals. Conclusion : The present data suggest that GBCT may play an important role in protecting brain tissues from chemical or ischemic injuries.

• Natural Product Sciences
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• v.22 no.4
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• pp.246-251
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• 2016

This study investigated the effects of (-)-sesamin on memory deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse model of Parkinson's disease (PD). MPTP lesion (30 mg/kg/day, 5 days) in mice showed memory deficits including habit learning memory and spatial memory. However, treatment with (-)-sesamin (25 and 50 mg/kg) for 21 days ameliorated memory deficits in MPTP-lesioned mouse model of PD: (-)-sesamin at both doses improved decreases in the retention latency time of the passive avoidance test and the levels of dopamine, norepinephrine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid, improved the decreased transfer latency time of the elevated plus-maze test, reduced the increased expression of N-methyl-D-aspartate (NMDA) receptor, and increased the reduced phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-response element binding protein (CREB). These results suggest that (-)-sesamin has protective effects on both habit learning memory and spatial memory deficits via the dopaminergic neurons and NMDA receptor-ERK1/2-CREB system in MPTP-lesioned mouse model of PD, respectively. Therefore, (-)-sesamin may serve as an adjuvant phytonutrient for memory deficits in PD patients.

• The Korean Journal of Nuclear Medicine
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• v.39 no.6
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• pp.421-429
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• 2005

Purpose: It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with $[^{11}C]raclopride$. Materials and Methods: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of $24.4{\pm}1.7$ years) were enrolled in this study $[^{11}C]raclopride$, a dopamine D2 receptor radioligand, was administrated with bolus-plus-constant infusion. Dynamic PET was performed during 120 minutes ($3{\times}20s,\;2{\times}60s,\;2{\times}120s,\;1{\times}180s\;and\;22{\times}300s$). following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar)/cerebellar activity, was measured under equilibrium condition at baseline and smoking session. Results: The mean decrease in binding potential of $[^{11}C]raclopride$ between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7%, 4.0% and 7.8%, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). Conclusion: These data demonstrate that in vivo imaging with $[^{11}C]raclopride$ PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount or nicotine administered bt smoking.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.11-18
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• 1994

Cyclic adenosine 3'5'-monophosphate (cyclic AMP) has been frequently accepted as an intracellular messenger for receptor-mediated action of opioids. In this experiment, it was designed to determine the interaction of dopaminergic and opioidergic system in the mouse striatum in normal and chronic haloperidol treated groups. Haloperidol 750ug/kg I.P. for 10 days was performed for dopamine denervation. The morphine, DAGO, DPDPE, and U5O,488H inhibited the increase of haloperidol-induced cyclic AMP content in chronic haloperidol treated mouse striatum. The inhibition of DAGO and DPDPE showed significant increase compared to normal mouse striatum. Naloxone showed antagonistic effect on the morphine and U5O,488H in chronic haloperidol treated group, and showed antagonistic effect on morphine, DAGO, DPDPE, and U5O, 488H in normal mouse striatum. These findings support that there is a functional interrelationship of dopaminergic and opioidergic pathway in the striatum. This result provides an evidence that following destruction of striatal dopaminergic neuron, there are some changes of cAMP content on the ${\mu},\;{\gamma},\;and\;{\kappa}$ opioid receptor, but the ${\kappa}$ opioid receptor still has its function.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.102-102
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• 2003

Embryonic stem (ES) cells proliferate extensively in the undifferentiated state and have the potential to differentiate into a variety of cell types in response to various environmental cues. The generation of functional dopaminergic neurons from ES cells is promising for cell replacement therapy to treat Parkinson's disease. We compared the in vitro differentiation potential of pluripotent human embryonic stem (hES, MB03) cells induced with basic fibroblast growth factor (bFGF) or retinoic acid (RA). Both types of treatment resulted in similar neural cell differentiation patterns at the terminal differentiation stage, specifically, 75% neurons and 11% glial cells. Additionally, treatment of hES cells with brain derived neurotrophic factor (BDNF) or transforming growth factor (TGF)- $\alpha$ during the terminal differentiation stage led to significantly increased tyrosine hydroxylase (TH) expression, compared to control (P<0.05). In contrast, no effect was observed on the rate of mature or glutamic acid decarboxylase-positive neurons. Immunostaining and HPLC analyses revealed the higher levels of TH (20.3%) and dopamine in bFGF and TGF-$\alpha$ treated hES cells than in RA or BDNF treated hES cells. The results indicate that TGF-$\alpha$ may be successfully used in the bFGF induction protocol to yield higher numbers of functional dopaminergic neurons from hES cells.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2007.04a
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• pp.147-153
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• 2007

Central to developing new treatment strategies for late onset sporadic Parkinson's disease (PD) and early onset familial PD is resolving the enigma of the specific vulnerability exhibited by substantia nigra dopamine (DA) neurons despite multiple risk factors. Neuropathological evidence from both human and experimental models of PD firmly supports a significant role for oxidative stress (OS) and mitochondrial dysfunction in the death of nigral DA neurons. Largely unknown are the genes underlying selective susceptibility of nigral DA neuron to OS and mitochondrial dysfunction and how they effect nigral DA cell death. To overcome the paucity of nigral DA neurons as well as the dilution effect of non-DA cells in brain tissues, we have developed wild type DA cell line model, SN4741 and mutant DJ-1 (-/-) DA cells, appropriate for microarray analysis and differential mitochondrial proteomics. Mutations in the DJ-1 gene (PARK7), localized in cytoplasm and mitochondria, cause autosomal recessive early onset PD. Through microarray analysis using SN4741 cells followed by validation tests, we have identified a novel phylogenically conserved neuroprotective gene, Oxi-a, which is specifically expressed in DA neurons. The knockdown of the gene dramatically increased vulnerability to as. Importantly as down-regulated the expression level of the gene and recovery of its expression via transient transfection exerted significant neuroprotection against as insult. We also have identified altered expression of mitochondrial proteins and other familial PD genes in DJ-1 (-/-) mutant cells by differential mitochondrial proteomics. In DJ-1 (-/-) cells the knockdown of the other familial PD genes (Parkin and PINK1) dramatically increased susceptibility to as. Thus, further functional characterization of the Oxi-$\alpha$ gene family and the mitochondrial alteration in the DJ-1 (-/-) cell model will provide the rationale for the neuroprotective therapy against both sporadic and familial PD.

• The Journal of Korean Medicine
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• v.19 no.1
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• pp.392-409
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• 1998

The present experiment was designed to examine the effects of Jeongjihwan on carecholamines, serotonin, amino acids, lipid peroxide, free radical scavenging activity, malondialdehyde and superoxide dismutase activity in senile brain. It was performed by administering Jeongjihwan extracts of a variety of concentration to senile rats to experimentally determine effects of Jeongjihwan on biochemical changes in senile brain and examine protective effects against neurotoxin. To examine survival rate, the rat's spinal cord sensory ganglion cell pretreated in Jeongjihwan extracts was cultured in oxygen free radical. The results were summarized as follows: 1. Jeongjihwan significantly increased noradrenaline in the hippocampus and hypothalamus of the brain tissue of senile rats, and even though Jeongjihwan increased noradrenaline also in other brain tissue, there was no significance. 2. Jeongjihwan had no effects on dopamine changes in all brain tissue of senile rats. 3. Jeongjihwan significantly increased serotonin, but decreased in other brain tissue. 4. Jeongjihwan increased amino acid in the brain tissue of senile rats. 5. Jeongjihwan significantly decreased lipid peroxide and free radical in the brain tissue of senile rats. 6. Jeongjihwan significantly increased survival rate of nerve cell exposed to oxygen free radical. According to the above results, Jeongjihwan is assumed to improve brain function by reacting on biochemical changes of the senile brain and carries effects of protecting against neurocytotoxicity, and that Jeongjihwan can be used to treat regressive brain disease carrying symptoms of psychoactive disorders.