• Journal of Oriental Neuropsychiatry
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• v.20 no.3
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• pp.283-295
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• 2009

Objectives : Parkinson's disease is a chronic neuron-degenerative disease. The medication of dopamine, one of the most common treatment for the disease, has effects of improving the symptom, but when taken for a long term, the medicine brings about side-effects such as the phenomenon of medicinal efficacy disappearance and dyskinesia. In addition, it doesn't have any effects in slowing down or stopping the development of Parkinson's disease. Methods : Accordingly, this study aims to investigate the clinical cases to stop or improve the development of Parkinson's disease by carrying out an independent treatment with Oriental medicine and a combined treatment with Western and Oriental medicines respectively for over 6 months. Results and Conclusions : The results of the study is expected to be an important precedent for the treatment of neuron-degenerative diseases of cranial nerve including Parkinson's disease in the future.

• Applied Microscopy
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• v.32 no.2
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• pp.175-183
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• 2002

In this study, we carried out immunostaining and immunogold labeling with rabbit anti-dopamine (TH) and rabbit anti-calbindin-$D_{28K}$ to examine the characteristics and functions of the neurons that secrete neurotransmitters in optic lobes of Todarodes pacificus and Octopus minor inhabiting the Korean waters. The obtained results are as follow. In the immunostaining with anti-dopamine, only a few of the large amacrine cells in an the upper part of an outer granule cell layer and the cells forming the islands of medulla showed positive reaction in Todarodes pacificus, while $2{\sim}3$ cells in the upper and middle parts of an outer granule cell layer and more than 5 cells in the islands of medulla reacted positively in Octopus minor. For the case of anti-calbindin case, $2{\sim}3$ small amacrine cells in the upper portion of the outer granule cell layer and $1{\sim}2$ cells which are located in the lower part of an inner granule cell layer showed positive reaction in Todarodes pacificus, while, in Octopus minor, 4 cells in the outer granule cell layer reacted positively, no immunoreactive cell being found in the inner granule cell layer. As a result of performing the immunogold labeling, relative large number ($17{\sim}26$) of gold particles were labeled per $0.5{\mu}m^2$ of the cytoplasm of the cells which showed the immunoreactivity to the anti-dopamine and anti-calbindin in Todarodes pacificus, however, small number (10) of gold particles were labeled in Octopus minor, which reach only half of the number in the Todarodes pacificus.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.2
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• pp.129-134
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• 2014

It has been suggested that transition metal ions such as iron can produce an oxidative injuries to nigrostriatal dopaminergic neurons, like Parkinson's disease (PD) and subsequent compensative increase of tetrahydrobiopterin ($BH_4$) during the disease progression induces the aggravation of dopaminergic neurodegeneration in striatum. It had been established that the direct administration of $BH_4$ into neuron would induce the neuronal toxicity in vitro. To elucidate a role of $BH_4$ in pathogenesis in the PD in vivo, we assessed the changes of dopamine (DA) and $BH_4$ at striatum in unilateral intranigral iron infused PD rat model. The ipsistriatal DA and $BH_4$ levels were significantly increased at 0.5 to 1 d and were continually depleting during 2 to 7 d after intranigral iron infusion. The turnover rate of $BH_4$ was higher than that of DA in early phase. However, the expression level of GTP-cyclohydrolase I mRNA in striatum was steadily increased after iron administration. These results suggest that the accumulation of intranigral iron leads to generation of oxidative stress which damage to dopaminergic neurons and causes increased release of $BH_4$ in the dopaminergic neuron. The degenerating dopaminergic neurons decrease the synthesis and release of both $BH_4$ and DA in vivo that are relevance to the progression of PD. Based on these data, we propose that the increase of $BH_4$ can deteriorate the disease progression in early phase of PD, and the inhibition of $BH_4$ increase could be a strategy for PD treatment.

• Molecules and Cells
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• v.26 no.3
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• pp.243-249
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• 2008

Corticotropin releasing factor (CRF) mediates various responses to stress through CRF receptors 1 and 2. CRF receptor 2 has two forms, $2{\alpha}$ and $2{\beta}$ each of which appears to have distinct roles. Here we used dopaminergic neuron-derived MN9D cells to investigate the function of CRF receptor 2 in dopamine neurons. We found that n-butyrate, a histone deacetylase inhibitor, induced MN9D cell differentiation and increased gene expression of all CRF receptors. CRF receptor $2{\beta}$ was minimally expressed in MN9D cells; however, its expression dramatically increased during differentiation. CRF receptor $2{\beta}$ expression levels appeared to correlate with neurite outgrowth, suggesting CRF receptor $2{\beta}$ involvement in neuronal differentiation. To validate this statement, we made a CRF receptor $2{\beta}$-overexpressing $MN9D/CRFR2{\beta}$ stable cell line. This cell line showed robust neurite outgrowth and GAP43 overexpression, together with MEK and ERK activation, suggesting MN9D cell neuronal differentiation. From these results, we conclude that CRF receptor $2{\beta}$ plays an important role in MN9D cell differentiation by activating the MEK/ERK signaling pathway.

• Interdisciplinary Bio Central
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• v.4 no.3
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• pp.6.1-6.12
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• 2012

Parkinson's disease (PD) is a complicated neurodegenerative disorder although it is oftentimes defined by clinical motor symptoms originated from age dependent and progressive loss of dopaminergic neurons in the midbrain. The pathogenesis of PD involves dopaminergic and nondopaminergic neurons in many brain regions and the molecular mechanisms underlying the death of different cell types still remain to be elucidated. There are indications that PD causing disease processes occur in a global scale ranging from DNA to RNA, and proteins. Several PD-associated genes have been reported to play diverse roles in controlling cellular functions in different levels, such as chromatin structure, transcription, processing of mRNA, translational modulation, and posttranslational modification of proteins. The advent of quantitative high throughput screening (HTS) tools makes it possible to monitor systemic changes in DNA, RNA and proteins in PD models. Combined with dopamine neuron isolation or derivation of dopamine neurons from PD patient specific induced pluripotent stem cells (PD iPSCs), HTS techonologies will provide opportunities to draw PD causing sequences of molecular events in pathologically relevant PD samples. Here I discuss previous studies that identified molecular functions in which PD genes are involved, especially those signaling pathways that can be efficiently studied using HTS methodologies. Brief descriptions of quantitative and systemic tools looking at DNA, RNA and proteins will be followed. Finally, I will emphasize the use and potential benefits of PD iPSCs-derived dopaminergic neurons to screen signaling pathways that are initiated by PD linked gene mutations and thus causative for dopaminergic neurodegneration in PD.

• YAKHAK HOEJI
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• v.57 no.2
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• pp.77-86
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• 2013

The neuroprotective effects of herbal ethanol extract (GP-EX) from Gynostemma pentaphyllum on dopamine neurons in animal model of Parkinson's disease (PD) were investigated. Rats and mice were administered with rotenone (2.5 mg/kg) for 28 days and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 30 mg/kg) for 5 days for the PD models, respectively and the animals were simultaneously treated with GP-EX (30 mg/kg, daily). After preparing the PD models, the animals were also administered with L-DOPA (10 mg/kg) for 14 days with or without GP-EX treatment. Treatment with GP-EX (30 mg/kg) inhibited the rotenone- and MPTP-induced neurotoxic effects in dopamine neurons of rats or mice, which was determined by the numbers of tyrosine hydroxylase-immunohistochemical staining survival cells, as well as the levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid. GP-EX (30 mg/kg) also showed the protective effects on neurotoxicity which was induced by long-term administration of L-DOPA (10 mg/kg) in rotenone- and MPTP-induced animal model of PD. The used doses of GP-EX (30 mg/kg) did not produce any signs of toxicity, such as weight loss, diarrhea, or vomiting, in rats and mice during the treatment periods. These results suggest that GP-EX has the protective functions against chronic L-DOPA-induced neurotoxic reactions in dopamine neurons of rotenone- and MPTP-induced animal model of PD. Therefore, the natural GP-EX may be beneficial in the prevention of PD progress and L-DOPA-induced neurotoxicity in PD patients.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.159-168
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• 1996

To determine the regulatory mechanism of phenylethanolamine N-methyltransferase (PNMT) in the adrenal gland and in central nervous system, we observed the change of enzyme activity and mRNA level of PNMT in the adrenal gland, the brain stem, and hypothalamus of rats, which were injected with two neuroleptic agents(reserpine and haloperidol ). Reserpine depleting catecholamines in presynaptic vesicle increased PNMT activities in the adrenal gland and the brain stem to 150% of the control in time-dependent manner, but not in the hypothalamus. Haloperidol blocking dopamine receptor decreased PNMT activities in the adrenal gland and the hypothalamus, but not in the brain stem. Thus, the results indicate that catecholamines inhibit synthesis of epinephrine in the brain stem and the adrenal gland, and that dopamine stimulates synthesis of epinephrine in the hypothalamus and the adrenal gland. In addition, since the change of mRNA levels were nearly in accordance with the change of activities, the transcriptional regulation of PNMT is considered the mechanism of the regulation of epinephrine neuron.

• Korean Journal of Veterinary Research
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• v.40 no.1
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• pp.1-16
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• 2000

Nowadays, mongolian gerbil is notably utilized for the research of brain and water deprivation because of a congenital incomplete willis circle structure in the brain, audiogenic seizure in low noise, and special cholesterol metabolism without water absorption for a long time. In this study, we are intend to identify the morphological changes of the catecholaminergic neuron of brain according to the time lapse in the condition of long term water deprivation. 55 mongolian gerbil were divided 10 groups(control, 1, 2, 3, 4, 5, 10, 15, 20, 42th day water deprivation group), of which each group include 5 mongolian gerbils and 5 normal mongolian gerbils in control group were also used for brain atlas as a control. The brains were observed by the immunohistochemical stain using the TH, DBH and PMNT antibody. The results were as followings; 1. The nerve fibers of the TH-immunoreactive neuron were observed only in the and corpus striatum of the telencephalon. 2. Intensity of the immunostain of the nerve fiber in the cerebral cortex and corpus striatum was decreased gradually day by day after water deprivation. 3. The TH-immunoreactive nerve cells were observed in the paraventricular and periventricular nucleus of the 3rd ventricular in the hypothalamus of mongolian gerbil but the number of nerve cells were decreased from the first day of the water deprivation to the 10th day and increased until the 20th day, after than redecreased from the 20th day by the continuous water deprivation. The number of nerve fibers in this area were increased in the first day, but decreased from the 2nd day of water deprivation. The shape and density of the dopamine secreting cells in the brain of mongolian gerbil by the immunoreactive stain were changed in the continuous water deprivation. In this results, we can conclude that dopamine concerned in the water metabolism of mongolian gerbil, and mongolian gerbil could be used as an animal model for the research of water deprivation.

• Korean Journal of Veterinary Research
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• v.60 no.4
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• pp.203-207
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• 2020

This study presents neuronal migration pattern of dopamine (DA) neurons generated in separate regions occupying the ventral mesencephalic territory. A single pulse 5-bromodeoxyuridine (BrdU) was administered at embryonic day (E)10-E15. Distribution of tyrosine hydroxylase (TH) positive cells was determined at E13-postnatal day 0 (P0) by immunohistochemistry. BrdU positive cells labeled at E10 were spread out uniformly in the mesencephalon from E13 to E15, migrating through dorsal and ventral routes at E17 and P0. TH expression labeled at E10 was observed at E13 in the ventromedial region and clearly formed in the ventral tegmental area (VTA) at E15. At E17, TH expression in the substantia nigra (SN) was observed in the ventrolateral region, spreading more outward of the mesencephalon at P0. Generation of TH-positive cells labeled at E13 was also observed in VTA and SN of the mesencephalon at E17 and P0. The expression of these cells labeled after E15 was markedly decreased. These results demonstrated that an almost complete primary structure of DA neuron was formed at the early embryonic stage in the ventral mesencephalon, showing the most active neuronal migration was occurred at E13-E17.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.721-729
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• 2018

GABAergic control over dopamine (DA) neurons in the substantia nigra is crucial for determining firing rates and patterns. Although GABA activates both $GABA_A$ and $GABA_B$ receptors distributed throughout the somatodendritic tree, it is currently unclear how regional GABA receptors in the soma and dendritic compartments regulate spontaneous firing. Therefore, the objective of this study was to determine actions of regional GABA receptors on spontaneous firing in acutely dissociated DA neurons from the rat using patch-clamp and local GABA-uncaging techniques. Agonists and antagonists experiments showed that activation of either $GABA_A$ receptors or $GABA_B$ receptors in DA neurons is enough to completely abolish spontaneous firing. Local GABA-uncaging along the somatodendritic tree revealed that activation of regional GABA receptors limited within the soma, proximal, or distal dendritic region, can completely suppress spontaneous firing. However, activation of either $GABA_A$ or $GABA_B$ receptor equally suppressed spontaneous firing in the soma, whereas $GABA_B$ receptor inhibited spontaneous firing more strongly than $GABA_A$ receptor in the proximal and distal dendrites. These regional differences of GABA signals between the soma and dendritic compartments could contribute to our understanding of many diverse and complex actions of GABA in midbrain DA neurons.