• 대한약리학회지
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• 제27권1호
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• pp.7-12
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• 1991

쥐(태령 14일) 뇌간 세포배양에서 발달과정에 따른 Tyrosine hydroxylase(TH) 활성 및 dopamine의 양적 증가를 전기화학 HPLC를 이용하여 측정하였다. TH 활성 및 dopamine의 양은 배양 7일까지 점차 증가하였다. 배양 7일째에 여러 약물들의 dopamine 대사에 대한 영향을 조사하였다. TH 억제제인 ${\alpha}-methyl-p-tyrosine$ 및 aromatic amiono acid decarboxylase 억제제인 NSD-1015는 효과적으로 dopamine을 고갈시켰다. Dopamine은 reserpine에 의해 고갈되었고, parglyine에 의해 증가되었다. 일주일 배양한 세포의 배양액에 tetrodotoxin$(0.1\;{\mu}M$)을 7일간 투여하였을 때 TH 활성은 현저히 감소하였다. 이상의 결과들은 배양세포의 dopamine 대사가 뇌 dopamine 대사를 충실히 반영함을 나타낸다. 뇌간 세포의 배양에서 HPLC-전기화학검출을 이용한 TH 활성 및 dopamine의 측정은 중추 dopamine계의 약리 및 독성 연구에 유용하리라 사료된다.

• 대한수의학회지
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• 제37권3호
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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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• 제27권4호
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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.

• 대한본초학회지
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• 제26권2호
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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.

• 한국한의학연구원논문집
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• 제6권1호
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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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• 제44권7호
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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.

• 한국발생생물학회지:발생과생식
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• 제15권2호
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• pp.143-150
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• 2011

이 연구는 수중 운동, 균형 훈련과 복합 운동이 파킨슨 유발 흰쥐 모델에 미치는 영향을 관찰하기 위해 수산화도파민(6-hydroxydopamine)을 흰쥐의 좌측 내측전뇌다발에 주사하여 파킨슨 모델을 제작하였다. 실험동물은 수중 운동을 적용한 실험군 I, 균형 훈련을 적용한 실험군 II, 복합 운동(수중 운동+균형 훈련)을 적용한 실험군 III, 수술 후 표준사육장에서 운동을 적용하지 않은 대조군으로 배치하였다. 수술 후 7일, 14일, 21일에 실험동물의 중뇌 흑질의 도파민 세포감소를 관찰하기 위하여 TH(tyrosine hydroxylase)의 발현 양상을 관찰하였고, 행동학적 검사로 수술 후 1일, 7일, 14일,21일에 아포몰핀유도 회전 검사를 실시하였다. 실험 결과, 실험군들에서 대조군에 비하여 유의하게 높은 TH 발현과 아포몰핀유도 회전수를 보였다. 하지만 실험군들 사이에는 유의한 차이가 나타나지 않았다. 이상의 결과에서 파킨슨유발 흰쥐모델이 기능 회복에 수중 운동과 균형 훈련이 효과적임을 알 수 있었으며, 흑질 치밀부의 도파민성 신경섬유의 증감을 나타내는 TH의 발현에도 수중 운동과 균형 훈련이 효과적임을 알 수 있었다.

• Natural Product Sciences
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• 제10권3호
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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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• 제33권4호
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• pp.291-298
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• 2003

스트레스는 교감신경계와 부신을 활성화시킨다. 본 연구에서는 고염식이가 흰 생쥐의 부신수질에 미치는 영향을 tyrosine hydroxylase (TH) 면역염색법과 투과 전자현미경을 이용한 미세구조적 관찰로 규명하였다. 1. 부신수질의 TH 면역반응은 고염식이 후 증가하였으며 특히 고염식이를 4주간 시행한 경우보다 4일간 시행한 흰 생쥐에서 더 강하게 관찰되었다. 2. TH 면역반응은 부신수질을 구성하는 세포들 중 노르아드레날린 세포의 세포질과 과립들에서 주로 나타났다. 3. 고염식이를 시행한 흰 생쥐 부신수질의 노르아드레날린 세포에서는 세포질 내에 비어있는 공간들, 분비과립이 팽대되어 과립 내 물질이 한 쪽으로 치우친 형태 및 손상된 미토콘드리아등의 특징들이 관찰되었다. 이와 같은 결과는 고염식이가 스트레스를 유발하는 요인이 될 수 있음을 시사해준다.

• 대한약리학회지
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• 제28권1호
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• pp.11-18
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• 1992

Physostigmine을 급성(0.75 mg/kg), 7일간 매일 1회(0.75 mg/kg) 그리고 7일간 연속(0.15 mg/kg/h) 투여한 쥐의 선조체에 있어서 dopamine(DA) 및 대사체와 tyrosine hydroxylase(TH)활성도의 변화를 검색하였다. 급성 투여 1시간 후 선조체의 DA 농도는 변화가 없었으나 dihydroxy-phenylacetic acid(DOPAC)과 homovanillic acid(HVA)농도는 증가하였다. 또한 DA의 turnover의 증가를 제시하는 DOPAC/DA와 HVA/DA의 비율도 증가하였다. 그러나 TH활성도는 24시간 후 감소를 나타내었다. Physostigmine을 매일 및 연속 투여군에서는 DA과 대사체의 농도에는 변화가 없었으나, DA의 turnover의 감소를 제시하는 DA과 대사체의 비율은 감소하였다. 그러나 TH활성도는 매일 투여군에서만 감소를 나타내었다. 이러한 결과는 physostigmine을 급성 및 아급성으로 투여시 dopamine대사의 변화가 있음을 제시한다. 또한 콜린 신경계의 아급성 자극은 dopamine 대사 및 활성도를 감소 시킬 가능성을 시사해 주었다.