• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.7-12
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• 1991

We measured the developmental increase of tyrosine hydroxylase(TH) activity and dopamine content with high performance liquid chromatography with electrochemical detection(HPLC-EC) in dissociated cultures of fetal rat brainstem(E14). TH activity and dopamine content increased progressively upto 7 days in vitro, when the effects of various drugs on the dopamine contents were studied. ${\alpha}-Methyl-p-tyrosine$, a TH inhibitor and NSD-1015, an inhibitor of aromatic amiono acid decarboxylase effectively depleted dopamine contents. Dopamine contents were depleted by reserpine and increased by pargyline. When cultures grown for 1 week in control medium were then exposed to tetrodotoxin$(0.1\;{\mu}M$) for 7 days, exposure to tetrodotoxin markedly decreased TH activity. All the above results indicate that dopamine metabolism in the cultered cells reflect reliably the property of brain dopamine metabolism. We suggest that measuring TH activity and dopamine content in brainstem culture with HPLC-EC can be useful tool in the study of pharmacology as well as toxicology of the central dopaminergic system.

• Korean Journal of Veterinary Research
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• v.37 no.3
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• pp.499-508
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• 1997

The distributions and morphological characteristics of neurons displaying immunoreactivity to the catecholamine synthetic enzymes, tyrosine hydroxylase(TH), dopamine-${\beta}$-hydroxylase(DBH), and phenylethanolamine-N-methyltransferase (PNMT) were examined in the adjacent sections of the olfactory bulb of the Striped Field Mouse(Apodemus agrarius coreae). None of these cell groups displayed either DBH or PNMT immunoreactivity. Many TH-immunoreactive neurons were present in the olfactory bulb. The vast majority of such cells occurred in the glomerular layer as periglomerular cells surrounding the glomeruli. Numerous addtional cells were present in the external plexiform layer, and scattered in the mitral cell layer and internal plexiform layer. Also TH-immunoreactive neurons were found in the glomerular layer and granular layer of the accessory olfactory bulb.

• Applied Microscopy
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• v.27 no.4
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• pp.461-472
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• 1997

The substantia nigra of the Mongolian gerbil was studies by tyrosine hydroxylase immunohistochemistry and immunoelectron microscopy with preembedding method. The purpose was to obtain information on the distribution and ultrastructure of the Tyrosine hydroxylase immunoreactive and dopaminergic neurons in the substantia nigra, in order to provide the necessary background for the gerbil. Large number of tyrosine hydroxylase immunoreactive neurons were located in the compact part of substantia nigra. Findings in the gerbil, compared to observations in the other species, included the presence of prominent bundles of tyrosine hydroxylase immunoreactive cytoplasmic processes passing in the dorsoventral direction from pars compacta into pars reticulata at middle and caudal levels of the substantia nigra, and the presence of a distinct tyrosine hydroxylase immunoreactive substantia nigra pars lateralis. Tyrosine hydroxylase immunoreactive neurons had well-developed cell organelles, especially rough endoplasmic reticulum, free ribosome and poly-ribosome, and showed the infoldings of the nuclear envelope. We anticipate that the present description of the cellular organization of the tyrosine hydroxylase immunoreactive dopaminergic area in the substantia nigra of gerbil will be useful for the animal experimental model of Parkinson's disease.

• The Korea Journal of Herbology
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• v.26 no.2
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• pp.59-66
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• 2011

Objectives : The goal of this study was to investigate the antidepressant effects of Mixture of Lycii Radicis Cortex and Moutan Cortex on the change of HPA-Axis and Catecholamic system. Methods : We were performed the Forced Swimming Test. The expressions of Corticotropin-Releasing Factor (CRF) and c-Fos at paraventricular nucleus (PVN), and tyrosine hydroxylase (TH) at ventral tegmental area (VTA) and locus coeruleus (LC) were evaluated by immunohistochemical method. Results : The duration of immobility in the Forced Swimming Test was significantly decreased in A100, A400(p<0.05~p<0.01). CRF expressions at PVN was significantly decreased in A400(p<0.05).No other group showed significant difference in expression of c-Fos at PVN comparing with control group. TH expressions at VTA was significantly decreased in A100 and A400, respectively(p<0.001). TH expressions at LC was significantly decreased in A100(p<0.01). Conclusions : According to the above results, Mixture of Lycii Radicis Cortex and Moutan Cortex has antidepressant effects via the reduction of CRF expression and the Catecholamine System activity.

• Korean Journal of Oriental Medicine
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• v.6 no.1
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• pp.99-105
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• 2000

Lithium, a simple monovalent cation, is the mainstay in the treatment of manic-depressive illness, but despite extensive research, its mechanism of action remains to be elucidated. Because lithium requires chronic administration for therapeutic efficacy and because its beneficial effects last well beyond its discontinuation, it has been postulated that lithium may exert major effects at the genomic level. We have previously shown that Yungmijihwangwon (YM) increase TH protein expression through antioxidant activity and unknown effects in vivo. In the pressent study, we have sought to determine if lithium in herbal medicine also increases the expression of endogenous gene known to be regulated by AP-1 and have therefore investigated the effects of herbal medicine on tyrosine hydroxylase (TH) levels. Male mice were treated with LiCl and herbal medicine for 30 days, and TH levels and dopamine level were measured in striatum using immunoblotting and ECD-HPLC. Herbal medicine treatment resulted in statistically nonsignificant increase in TH levels in mouse striatum. The precise therapeutic relevance of these effects is presently unknown.

• Molecules and Cells
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• v.44 no.7
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• pp.493-499
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• 2021

Parkinson's disease (PD) is characterized by a progressive loss of dopamine-producing neurons in the midbrain, which results in decreased dopamine levels accompanied by movement symptoms. Oral administration of l-3,4-dihydroxyphenylalanine (L-dopa), the precursor of dopamine, provides initial symptomatic relief, but abnormal involuntary movements develop later. A deeper understanding of the regulatory mechanisms underlying dopamine homeostasis is thus critically needed for the development of a successful treatment. Here, we show that p21-activated kinase 4 (PAK4) controls dopamine levels. Constitutively active PAK4 (caPAK4) stimulated transcription of tyrosine hydroxylase (TH) via the cAMP response element-binding protein (CREB) transcription factor. Moreover, caPAK4 increased the catalytic activity of TH through its phosphorylation of S⁴⁰, which is essential for TH activation. Consistent with this result, in human midbrain tissues, we observed a strong correlation between phosphorylated PAK4^S474, which represents PAK4 activity, and phosphorylated TH^S40, which reflects their enzymatic activity. Our findings suggest that targeting the PAK4 signaling pathways to restore dopamine levels may provide a new therapeutic approach in PD.

• Development and Reproduction
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• v.15 no.2
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• pp.143-150
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• 2011

The objective of this study was to determine the effect of exercise on a hemiparkinsonian rat model. Nigrostriatal dopamine cell lesions were produced by injecting 6-hydroxydopamine at the left medial forebrain bundle of rats. In this study, the rats were divided into the following 4 groups: the control group without any exercise, experimental group I with aqua-exercise (Exp I), experimental group II with balance exercise (Exp II) and experimental group III with complex exercise (aqua-exercise+balance exercise; (Exp III)). Exercises were applied to all the experimental groups after the operation. In order to observe the dopaminergic cell loss, we assessed the level of tyrosine hydroxylase (TH) expression in the midbrain of rats, and performed the apomorphine-induced rotation test at postoperative days (PDs) 7, 14, and 21. Experimental groups had significantly higher TH-immunoreactivity and behavioral performance than the control group. However, there was no difference in TH-immunoreactivity and behavioral performance across the experimental groups. These results suggest that the application of aqua-exercise and balance exercise could suppress dopaminergic cell loss in the substantia nigra of rat brains and could increase behavioral recovery in hemiparkinsonian rats.

• Natural Product Sciences
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• v.10 no.3
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• pp.114-118
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• 2004

It is reported that $(1R,9S)-{\beta}-Hydrastine$ hydrochloride (BHSH) decreased the intracellular dopamine content by inhibiting tyrosine hydroxylase (TH) activity in PC12 cells. In this study, the inhibitory mechanisms on TH activity by BHSH in PC12 cells were investigated. BHSH treatment caused a reduction of TH activity and TH mRNA level in a dose-dependent manner. After the treatment of $20\;{\mu}M$ BHSH, TH activity and TH mRNA content were reduced at 15 min, reached the minimal levels at 6-24 h, and then recovered gradually to the control level. BHSH at $10-50\;{\mu}M$ caused a decrease in the basal intracellular cyclic AMP levels at 10 min in a concentration-dependent manner. In addition, BHSH at $20-100\;{\mu}M$ decreased the basal intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ immediately in a dose-dependent manner. BHSH also inhibited the 56 mM $K^+ $ depolarization-induced elevation in $[Ca^{2+}]_i$, and blocked caffeine-activated store-operated $Ca^{2+}$ entry in PC12 cells. These data suggest that BHSH inhibits TH activity and TH gene expression, in part, through reducing cyclic AMP content and basal $[Ca^{2+}]_i$ in PC12 cells.

• Applied Microscopy
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• v.33 no.4
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• pp.291-298
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• 2003

Exposure to stressful stimuli is known to activate the peripheral sympathetic nervous system and the adrenal gland. In this study, we evaluated the effects of high-salt diet on the mouse adrenal medulla using the tyrosine hydroxylase (TH) immunohistochemistry and the transmission electron microscopic observation. Immunoreactivity for TH was increased after high-salt diet. Especially, the TH immunoreactivity was stronger in 4 days high-salt diet mouse than that of 4 weeks. TH immunoreactivity was mainly present in the cytoplasm and granules of the noradrenaline cells. After high-salt diet, the noradrenaline cells exhibited the ultrastructural alterations consisting of areas of empty cytoplasm, expanded granules, and some damaged mitochondria. These results suggest that high-salt diet may be a factor of stressful stimuli on the mouse.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.11-18
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• 1992

Rats were treated with physostigmine, using 0.75 mg/kg acutely, with 0.75 mg/kg daily for 7 dats, or with 0.15 mg/kg/h continuously for 7 days. Striatal dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels and tyrosine hydroxylase (TH) activities were studied. After acute treatment striatal DOPAC and HVA concentrations were significantly increased without changes in DA level 1 h, but not 24 h. And also the ratios of DOPAC/DA and HVA/DA were increased, suggesting an increased turnover of DA. however TH activities were decreased 24h, but not 1h after acute administration. After both daily and continuous treatment with physostigmine for 7 days, neither DA nor its metabolites were changed. However their ratios were decreased, suggesting a decreased turnover of DA. The TH activities were only decreased in the daily treated group, but not in the continously treated one. These results indicate that dopamine metabolisms are changed after acute and subacute administration with physostigmine. Further it suggest that the subacute stimulation of cholinergic activity may induce the dopamine metablism and activity to be decreased.