• The Journal of Korean Medicine
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• v.26 no.4
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• pp.98-107
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• 2005

Objectives: Acupuncture treatment has been clinically used for functional recovery in Parkinson's disease. In the present study, we investigated the effect of acupuncture at Zusanli (ST36) on nigrostriatal dopaminergic neuronal cell death in rats. Methods: A Parkinson's disease model was induced by the unilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum. Acupuncture treatment was performed at Zusanli (ST36) and at the hip, as a non-acupoint, once a day for 14 days. Two weeks after 6-0HDA injection, an apomorphine-induced rotational behavior test showed significant rotational asymmetry in rats with Parkinson's disease. Immunostaining for tyrosine hydroxylase demonstrated a dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. Results: Acupuncture at the ST36 acupoint significantly inhibited rotational asymmetry in rats with Parkinson's disease, and also protected against 6-OHDA-induced nigrostriatal dopaminergic neuronal loss. These effects of acupuncture were not observed for non-acupoint acupuncture. Conclusions: The present study shows that acupuncture treatment, especially at the ST36 acupoint, can be used as a useful strategy for the treatment of Parkinson's disease.

• Herbal Formula Science
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• v.18 no.1
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• pp.155-167
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• 2010

Objectives : In order to investigate the antidepressant effects of Forsythiae Fructus(FF), we performed the Forced Swimming Test(FST). Also the expressions of corticotropin-releasing factor (CRF), c-Fos and tyrosine hydroxylase(TH) were measured by immunohistochemical method at paraventricular nucleus(PVN), ventral tegmental area(VTA) and locus coeruleus(LC). Methods : Spraque-Dawley rats were administered FF extract(100 mg/kg, 400 mg/kg) intragastrically three times prior to the FST. Results : The duration of immobility in the FST was significantly decreased in the FF 100 mg/kg, 400 mg/kg groups(p<0.05). The expression of CRF was significantly reduced in the FF 100 mg/kg and 400 mg/kg groups(p<0.001). c-Fos expression was significantly decreased at PVN in the FF 100 mg/kg group(p=0.069). TH expression at VTA was significantly increased in the FF 100 mg/kg and 400 mg/kg groups(p<0.05). TH expression at LC was not significantly changed(p=0.346). Conclusion : According to the results, it can be suggested that Forsythiae Fructus has antidepressant effect via the decreased immobility through the reduction of CRF and c-Fos expression at PVN.

• Natural Product Sciences
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• v.24 no.2
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• pp.99-102
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• 2018

This study investigated the effects of ombuoside, a flavonol glycoside, on dopamine biosynthesis in PC12 cells. Ombuoside at concentrations of 1, 5, and $10{\mu}M$ increased intracellular dopamine levels at 1 - 24 h. Ombuoside (1, 5, and $10{\mu}M$) also significantly increased the phosphorylation of tyrosine hydroxylase (TH) (Ser40) and cyclic AMP-response element binding protein (CREB) (Ser133) at 0.5 - 6 h. In addition, ombuoside (1, 5, and $10{\mu}M$) combined with L-DOPA (20, 100, and $200{\mu}M$) further increased intracellular dopamine levels for 24 h compared to L-DOPA alone. These results suggest that ombuoside regulates dopamine biosynthesis by modulating TH and CREB activation in PC12 cells.

• YAKHAK HOEJI
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• v.29 no.4
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• pp.165-175
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• 1985

It has been reported that clonidine is $\alpha_2$-adrenergic agonist, potnet new hypotensive drug in human with low dose. The change in blood pressure is implicated in the concentration, release, uptake and metabalism of catecholamine and activity of catecholamine synthesizing enzyme in specific brain areas. Thus the experiment was set up to investigate the effect on the enzyme activity of clonidine alone and that of clonidine pretreated with imipramine or tranylcypromine by measuring activity of the Dopa-forming enzyme, tyrosine hydroxylase (TH) and epinephrine forming enzyme, phenylethanolamine-N-methyl transferase (PNMT) in brain and adrenal gland. The TH activity in brainstem and substantia nigra is decreased by intraperitoneally administered clonidine 0.1mg/kg twice a day for 5 days, but increased in the rats pretreated with imipramine 10mg/kg intraperitoneally given 26 hrs and 5 hrs before decaptitation. However the TH activity in all regions of brain is increased in rats pretreated with tranylcypromine 10mg/kg intraperitoneally twice a day for 5 days. The effect of clonidine on TH activity is due to inhibition release of norepinephrine by activation of presynaptic $\alpha_2$-adrenoreceptor, axon terminal result in the decrease of TH activity in brain. The increasing of TH activity in brain results in attenuation of the role of clonidine by pretreated with imipramine or tranylcypromine in rats. The activity of PNMT was not significantly affected by clonidine, imipramine and tranylcypromine in adrenal gland.

• 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.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.90-97
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• 2022

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson's disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1189-1196
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• 2023

This study proposed to demonstrate the neuroprotective effects of heat-killed Levilactobacillus brevis KU15152. Heat-killed L. brevis KU15152 showed antioxidant activity similar to that of Lacticaseibacillus rhamnosus GG, in terms of radical scavenging activity. To evaluate the neuroprotective effects, conditioned medium (CM) obtained by incubating heat-killed bacteria in intestinal cells (HT-29) was used through gut-brain axis. CM from L. brevis KU15152 protected neuroblastoma cells (SH-SY5Y) against H₂O₂-induced oxidative stress. Pretreatment with CM significantly alleviated the morphological changes induced by H₂O₂. Heat-killed L. brevis KU15152 showed an increased brain-derived neurotrophic factor (BDNF) expression in HT-29 cells. L. brevis KU15152-CM remarkably downregulated the Bax/Bcl-2 ratio, while upregulating the expression of BDNF and tyrosine hydroxylase (TH) in SH-SY5Y cells. Furthermore, L. brevis KU15152-CM reduced caspase-3 activity following H₂O₂ treatment. In conclusion, L. brevis KU15152 can be potentially used as food materials to avoid neurodegenerative diseases.

• Journal of Environmental Science International
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• v.32 no.10
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• pp.723-729
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• 2023

Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neuronal loss in the substantia nigra, resulting in reduced dopamine levels and consequent motor dysfunction. Genetic and environmental factors contribute to oxidative stress in PD. Cicadidae Periostracum (CP), a traditional Korean medicine, has shown neuroprotective effects against MPTP-induced neurotoxicity in PD. However, its effects on the 6-hydroxydopamine (6-OHDA) model have not been established. This study examined CP's effects on a 6-OHDA-induced PD model. CP protected against 6-OHDA damage in both in vitro and in vivo studies. Furthermore, CP reduced the production of reactive oxygen species, inhibited apoptosis, preserved dopamine levels, protected tyrosine hydroxylase in the substantia nigra, and improved motor function. These findings suggest that CP may delay PD progression by maintaining the redox balance.

• Development and Reproduction
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• v.6 no.2
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• pp.105-110
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• 2002

Numerous hormones are involved in the regulation of reproduction. Among them, estrogen and progesterone are the most important ovarian steroid hormones regulating female fertility. On the other hand, diverse stressors impede female receptivity and fertility. Since norepinephrine(NE) and epinephrine(E) are released from the adrenal during stress, it might play a role in stress-induced disruptions of fEmale reproductive parameters. The present study was performed to analyze the changes in adrenal catecholaminergic activities in cycling rats. The tissue content and secretion level of catecholamines were determined by high performance liquid chromatography coupled with electrochemical detector(HPLC-ECD). Adrenomedullary content of norepinephrine(NE) was increased on proestrus stage (59.47 $\pm$ 6.86 ug/gland), peaked on diestrus I stage(65.22 $\pm$ 5.99 ug/gland), and was nadir on diestrus II stage(41.63 $\pm$ 1.33 ug/gland). The highest E content was observed on proestrus stage(361.86 $\pm$ 15.58 ug/gland) while the lowest level was on diestrus II stage(285.58 $\pm$ 12.25 ug/gland). In addition to these observations, a significant reduction of the NE : E ratio was observed (1 : 4.81 on diestrus I vs 1 : 6.13～7.02 on other stages). In vitro secretion of adrenal NE and E was increased on proestrus stage, peaked on estrus stage, and decreased on diestrus II stage. Interestingly, the NE : E ratio in conditioned media was significantly increased on estrus stage (1 : 3.32 vs 1 : 2.34～2.65 on other stages. The biosynthesis of NE and E is mediated by tyrosine hydroxylase(TH) and phenylethanolamine-N-methyltransferase(PNMT) which acts conversion of tyrosine into DOPA and NE into E, respectively. These finding demonstrated that sex steroids, during setrous cycle, seem to be able to modify the adrenal catecholamines biosynthesis and secretion with stage-specific manner by modulation of the enzyme activities.

• KSBB Journal
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• v.20 no.5 s.94
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• pp.363-370
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• 2005

Neural stem cells (NSCs) of the central nervous system (CNS) have raised a great interest not only for their importance in basic neural development but also for their therapeutic potentials in neurologically degenerative diseases such as Parkinson's, Alzheimer and stroke. During the CNS development, two molecular cascades determine specification of midbrain dopamine system. In one pathway, FGF-8, sonic hedgehog and transcription factor Nurr1 specify dopamine neurotransmitter phenotype. In the other, transcription factors $Lm{\times}lb\;and\;Pt{\times}3$ are required for induction of dopaminergic neurons. In Nurr1 knockout mouse, tyrosine hydroxylase (TH) positive cells fail to appear in substantia nigra, indicating that Nurr1 is essential in specification of dopaminergic cell phenotype. In this study, we used the immortalized human NSCs retrovirally transduced with Nurr1 gene to probe the Nurr1 mediated mechanism to induce dopamine phenotype. While Nurr1 over-expression alone did not generate dopamine phenotype in NSCs, applications of retinoid and forskolin induced expression of TH and AADC mRNAs. In addition, co-cultures of Nurr1 expressing NSCs with human astrocytes induced a marked increase of TH expression. In this co-culture system, the addition of retinoid and forskolin dramatically increased expression of TH. These results indicate that the immortalized human NSCs with Nurr1 gene could have a clinical utility for cell replacement for the Parkinson patients.