• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1996년도 춘계학술대회
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• pp.216-216
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• 1996

The purpose of the present study was to determine whether in vivo noradrenergic neural activity in the locus coeruleus is related to the development of hypertension. Two groups of animals were prepared, 1) young spontaneously hypertensive rats (SHR) and 2) age-matched normotensive wistar kyoto rats (WKY). At il weeks of age, the release of norepinephrine (NE) and 3,4-dihydroxyphenylglycol (DOPEG) from locus coeruleus of young SHR and WKY as an index of neural activity were determined by in vivo microdialysis along with blood pressure (BP) at three conditions : 1) normal; 2) elevated BP by systemic injection of phenylephrine and 3) alpha-1 adrenoceptor stimulated by perfusion of phenylephrine into the locus coeruleus through microdialysis probe. Basal releases of NE and DOPEG from the iocus coeruleus were 0.415+/-0.089pg/20min, 1.311+/-0.293 pg/20min in SHR and 0.204+/-0.078 pg/20min, 1.492+/-0.365 pg/20min in WKY respectively. Basal release of NE from the locus coeruleus of SHR was significantly greater than that of WKY. Phenylephrine systemic injection caused elevation of BP in both SHR and WKY in a dose related manner. Following phenyephrine injection, the releases of NE and DOPEG from the locus coeruleus of SHR were significantly decreased, whereas there were no significant changes in the releases of NE and DOPEG In young WKY. Alpha-1 adrenoceptor stimulation in the locus coeruleus by perfused phenylephrine through microdialysis probe caused pressor responses in both SHR and WKY, but the magnitude of pressor response in SHR was larger compared with that in WKY. The result from the present study suggests that noradrenergic neural activity in locus coeruleus may contribute as one of triggering factors for the expression of hypertension in young SHR.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 제3회 추계심포지움
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• pp.115-124
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• 1995

The purpose of the present study was to address whether the in vivo noradrenergic neural activities in the locus coeruleus are involved in the regulation of blood pressure. Two groups of the animals were prepared, 1) SHR and 2) age-matched normotensive control, WKY. At the age of 6 and 16 weeks, blood pressure and the releases of NE from the locus coeruleus in SHR and KWY were measured by in vivo microdialysis at three different conditions: 1) normal, 2) elevated state of blood pressure by systemic injected phenylephrine and 3) increased state of neural activity by perfused phenylephrine into the locus coeruleus. The basal release of NE of SHR were significantly higher than that of WKY, Phenylephrine treatment caused elevation of blood pressure in both SHR and WKY in dose-dependent manner. Following phenylephrine injection, the releases of NE from the locus coeruleus of SHR were significantly decreased, whereas the significant change of NE in WKY was observed in the highest dose of phenylephrine. Phenylephrine perfusion into the locus coeruleus through microdialysis probe caused pressor responses and the pressor response in SHR was greater compared with that in WKY. The results from the present study suggests that the noradrenergic nervous system in the locus coeruleus may contribute as one of the development and maintenance factors for hypertension in SHR.

• Biomolecules & Therapeutics
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• 제5권4호
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• pp.336-343
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• 1997

The purpose of the present study was to address whether the in vivo noradrenergic neural activities in the locus coeruleus are related to the development of hypertension. Two groups of the animals were prepared, 1) young SHR and 2) age-matched normotensive control, WKY. At the age of 6 weeks, blood pressure and the releases of NE and DOPEG from the locus coeruleus in young SHR and WKY were measured by in vivo microdialysis at two different conditions; 1) normal and 2) elevated state of blood pressure by systemically injected phenylephrine. Basal releases of NE and OOPEG from the locus coeruleus were $0.415 \pm$0.089 pg/20 min and $1.311 \pm0.293$ pg/20 min in SHR and $0.204\pm0.078$ pg/20 min and $1.472\pm 0.365$ pg/20 min in WKY The basal release of NE of SHR was significantly greater than that of WKY. Phenylephrine treatment caused elevation of blood pressure in both SHR and WKY in dose-dependent manner. Following phenylephrine injection, the releases of NE and DOPEG from the locus coeruleus of SHR were significantly decreased, whereas there was no significant changes of NE in WKY. The results from the present study suggests that the noradrenergic nervous system in the locus coeruleus may contribute as one of the triggering factors for the expression of hypertension in young SHR.

• Animal cells and systems
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• 제8권3호
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• pp.221-229
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• 2004

The projections from the dorsal raphe (DR) to the locus coeruleus (LC) or vice versa were analyzed in the rat using an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L) combined with serotonin (5-hydroxytryptamine, 5-HT) or dopamine-beta-hydroxylase (DBH) immunostaining. Following the injection of PHA-L into the middle DR, DR-originating fibers with varicosities have contacted DBH-immunolabeled cells in the rostral, middle, and caudal LC. Axon terminals were also observed in the subcoeruleus nucleus. When the PHA-L injection was confined within the caudal DR, axonal fibers with varicosities were observed mainly at the rostral pole of the LC. Following the injection of PHA-L into the caudal, principal LC, labeled fibers with varicosities have contacted 5-HT-immunolabeled neurons at dorsomedial, ventromedial, lateral wing, and caudal sub-divisions of the DR. The present anterograde study suggests that the DR or the LC nuclei communicate with each other in order to perform a variety of functions including vigilance, analgesia, and stress responses.

• KSBB Journal
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• 제18권3호
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• pp.207-210
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• 2003

Locus coeruleus (LC)에는 전체 노르아드레날린성 뉴런의 절반 가량이 모여 있는데, 여기서 노르아드레날린성 뉴런이 뇌의 거의 모든 부위로 신경자극을 보내게 된다. LC는 알츠하이머병, 파킨슨병, 헌팅턴병 같은 여러 가지 신경퇴행성 질환에서 공통적으로 타격을 받는 주요 부위이다. 뇌 유래 신경영양인자, BDNF가 LC 노르아드레날린성 뉴런을 포함한 중추신경계 뉴런들의 분화와 신경세포 생존에 중요한 조절자로 작용한다. 본 연구에서는 LC 노르아드레날린성 신경세포에서 여러 가지 작은 분자들과 성장인자들이 BDNF 생산을 촉진할 수 있는지를 조사하였다. 실험에 사용한 분자들로는 neuropeptides, cytokines, 성장인자, 신경전달물질들과 세포내 신호전달물질들이 포함되었다. 여러 가지 작은 분자들과 성장인자들 중에서 FGF8b, BMP-4, forskolin 그리고 dibutyrl cGMP가 LC 노르아드레날린성 뉴런에서 BDNF 분비를 뚜렷하게 증대시킨 것으로 판명되었다. 특히, BMP-4는 BDNF 생산을 2.5배 이상 증가시켰다. LC 노르아드레날린성 뉴런에서 BDNF를 증가시킨 물질들은 여러 가지 신경퇴행성 질환에서 신경세포가 손실되는 것을 막거나 지연시킬 수 있을 것이므로, 치료제나 증상완화제로서의 가능성이 높다.

• Animal cells and systems
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• 제7권1호
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• pp.49-55
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• 2003

The fiber projection from the prefrontal cortex to the locus coeruleus (LC) in the periventricular region was analyzed in rat using anterograde and retrograde tracing methods. Following injection of an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L), into prelimbic and infralimbic regions of the medial prefrontal cortex, labeled axonal fibers with varicosities were observed bilaterally within the LC, with ipsilateral predominance. Terminal labeling was also observed in the region medial to the nucleus at rostral to middle levels of the LC, whereas axonal labeling in the caudal LC was minimal. Anterogradely-labeled axonal fibers were not found in the subcoerulear region. A retrograde tracer, gold-conjugated and inactivated wheatgerm-agglutinin horseradish-peroxidase (WGA-apo-HRP-gold), was injected into several rostro-caudal levels of the LC. Majority of retrogradely-labeled cells were observed in the prelimbic or infralimbic regions of the medial prefrontal cortex when the injections were made into rostral to middle levels of the LC. Only a few cells were observed in cingulate, dorsal peduncular, orbital, or insular cortices. The present findings suggest that the nucleus LC receives restricted, excitatory inputs from cognitive, emotional, and autonomic centers of the cerebral cortex and might secondarily have influences on widespread brain regions via its diversified monoaminergic innervation.

• 대한수의학회지
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• 제40권3호
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• pp.451-461
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• 2000

The locus coeruleus(LG) is known to be observed a sexual dimorphism in rat CNS. LC is the largest collections of norepinephrine(NE)-containing neurons in the mammalian brain. Especially in rat, all LC neurons contained NE unlike other mammalians, so that specific reactions were found in the tyrosine-hydroxylase(TH) immunoreactive neurons. Sexual dimorphism of rat LC has affected by genes before sex hormone appeared, thereafter affected by sex hormones. In these day, many scientists founded morphological differences between male and female LC morphology, but differences of entire structure was not founded. Thus we investigated sex differences of the LC neuron's morphology in rat by three-dimensional(3-D) reconstruction using Confocal laser scanning microscopy(CLSM). We reported that neuron's shape was relatively-large multipolar neurons and neuron's processes in dorsal LC proceeded to ventral direction in the male and female rat. Male had a longer anterior-posterior length than female had in dorsal LC. In addition to middle-LC, male rat's LC had a more thicker posterior region but had not viewed in a previous study. In reverse, female rat's LC had a thicker anterior region like a previous study. This results using 3-D reconstruction by CLSM showed that the male's LC was more wide-ranging than female's relatively.

• 대한본초학회지
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• 제22권2호
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• pp.127-135
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• 2007

Objective : Investigation of the anti-stress effects of Sihosogansan Methods : Passive avoidance test(PAT) was performed after applying immobilization stress in water to rats. Also, forced swimming test(FST) was performed to another rats and after FST, the degree of Tyrosine Hydroxylase(TH) expression was measured with immunohistochemical method in the regions of locus coeruleus(LC) and ventral tegmental area (VTA). Results : In the PAT after immobilization stress in water, response latency was significantly increased in the Sihosogansan(400mg/kg) group in comparison with the control group. In the FST, immobility was significantly decreased in the Sihosogansan groups (100mg/kg, 400mg/kg), comparing with the control group. Stress-induced TH increases were suppressed in the Sihosogansan groups (100mg/kg, 400mg/kg) at the LC and the VTA region respectively. Conclusion : Sihosogansan can improve memory ability of rats, reduce behavior of depression in rats, decrease TH-immunoreactive cells at the LC and VTA region in rat, and it may be concluded that Sihosogansan has significant effect in reducing stress.

• BMB Reports
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• 제29권5호
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• pp.393-397
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• 1996

Sprague-Dawley male rats (150 g) were chronically treated with 5 v/v % ethanol admixed with nutritionally complete liquid diet and fed ad libitum for 3 weeks. Controls were pair fed with the isocaloric sucrose liquid diet. One half of each group was exposed to cold stress at $4^{\circ}C$ either for 24 h (for determination of mRNA by in situ hybridization) or for 48 h (for determination of enzyme activity). Chronic ethanol treatment (ethanol) did not affect tyrosine hydroxylase (TH) mRNA level in locus coeruleus (LC) of brain and adrenal medulla (AM) compared to controls. Cold stress showed strong increase of TH mRNA level in LC and AM compared to controls. Pretreated ethanol reduced the increased TH mRNA level by cold stress in LC and AM. Ethanol did not affect TH activity in LC and adrenal glands (adrenals). Cold stress increased TH activity in LC but not in adrenals. Pretreated ethanol did not reduce the increased TH activity by cold stress in LC but this result was not shown in adrenals. It is suggested that ethanol does not affect the message level and enzyme protein level for TH in LC and AM in normal rat. It is also hypothesized that pretreated ethanol reduces the magnitude of acute cold stress response, that is induction of TH mRNA in LC and AM, and does not reduce the increased TH enzyme protein that is also acute cold stress response in LC.

• 수면정신생리
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• 제2권2호
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• pp.133-137
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• 1995

The author reviews current knowledge about what REM sleep is and where and how it is generated. REM sleep is the state in which our most vivid dreams occur. REM sleep is identified by the simultaneous presence of a desynchronized cortical EEG, an absence of activity in the antigravity muscles(atonia), and periodic bursts of rapid eye movements. Another characteristic phenomena of REM sleep are the highly synchronized hippocampal EEG of theta frequency and the ponto-geniculo-occipital(PGO) spike. All these phenomena can be explained in terms of changes in neuronal activity. Transection studies have determined that the pons is sufficient for generating REM sleep. Lesion studies have identified a small region in the lateral pontine tegmentum corresponding to lateral portions of the nucleus reticularis pontis oralis(RPO) and the region immediately ventral to the locus coeruleus, which is required for REM sleep. Unit recording studies have found a population of cells within this region that is selectively active in REM sleep. Cholinergic neurons of the giant cell field of pontine tegmentum(ETG), which is 'REM a sleep-on cells', has shown to be critically involved in the generation of REM sleep. Noradrenergic neurons of the locus coeruleus and serotonergic neurons of the dorsal raphe, which are called 'REM sleep-off cells', appear to act in a reciprocal manner to the cholinergic neurons. It is proposed that the periodic cessations of discharge of 'REM sleep-off cells' during REM sleep might be significant for the prevention of the desensitization of receptors of these neurons.