• Molecules and Cells
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• 제41권8호
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• pp.742-752
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• 2018

Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.

• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2006년도 The 6th Intermational Symposium on Developmental Biotechnology
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• pp.62-62
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• 2006

• 한국동물학회:학술대회논문집
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• 한국동물학회 2003년도 한국생물과학협회 학술발표대회
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• pp.165.4-165
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• 2003

No Abstract, See Full Text

• 수면정신생리
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• 제16권1호
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• pp.5-9
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• 2009

Relatively little is known about the neurobiology of insomnia, despite its wide prevalence and broad medical impact. Although much is still to be learned about the pathophysiology of the disorder, identification, systematic assessment, and appropriate treatment are clearly beneficial to patients. Recent research, using quantitative EEG, polysomnography (PSG), multiple sleep latency test (MSLT) and neuroimaging techniques, suggests that some broad areas can be identified as possible pathophysiological models. Sleep-wake homeostat model hypothesizes a failure in homeostatic regulation of sleep, an attenuated increase in sleep drive with time awake, and/or defective sensing of sleep need. Circadian clock model hypothesizes a dysfunctional circadian clock, resulting in changes in the timing of sleep-wake propensity that are incompatible with normal sleep. Intrinsic sleep-wake state mechanism model suggests that abnormal function of insomnia comprises the systems responsible for expression of the sleep states themselves. Extrinsic over-ride mechanism (stress-response) model suggests that insomnia reflects the consequences of overactivity of one of the systems considered "extrinsic" to normal sleep-wake control. Many current therapies for insomnia are based on these physiological models. Several attempts have been made to create a physiological model that would explain this disorder and could be used as a foundation for treatment. However, it appeared that no model can fully explain and clarify all aspects of insomnia. Future research should be necessary to expand our knowledge on the biological dimensions of insomnia.

• 한국임상약학회지
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• 제6권2호
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• pp.1-6
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• 1996

Carcadian rhythm dependence of vancomycin pharmacokinetics was evaluated in 5 normal volunteers receiving a single intravenous 1.0 g dose of vancomycin at 8 o'clock in the morning and another occasion at 8 o'clock in the evening in a crossover manner. The serum data were subjected to simultaneous computer nonlinear least squares regression analysis using a two-compartment pbarmacokinetic model. The mean half-life of vancomycin was $4.78\pm0.81$ hr in the morning and $4.25\pm0.51$ hr in the evening. The mean total body clearance of vancomycin was $1.29\pm0.58$ hr in the morning and $5.58\pm0.48$ hr in the evening. No circadian rhythm was found to be apparent in normal volunteers. The mean in intrasubject difference in the half-life between 8 A.M. and 8 P.M. was $15.4\%$ with fluctuations ranging from $10.4\sim33.8\%$, It is reasonable to consider individual circadian rhythm for effective dosage regimen of vancomycin in clinical chronotherapeutics.

• Biomolecules & Therapeutics
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• 제19권3호
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• pp.308-314
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• 2011

It has been shown that circadian genes not only play an important role on circadian rhythms, but also participate in other physiological and pathological activities, such as drug dependence, cancer development and radiation injury. The Per2, an indispensable component of the circadian clock, not only modulates circadian oscillations, but also regulates organic function. In the present study, we applied mPER2-upregulated NIH3T3 cells to reveal the relationship of mPer2 and the cells damaged by ultraviolet C (UVC). NIH3T3 cells at the peak of the expression of mPer2 induced by phorbol 12-myristate 13-acetate (PMA) demonstrated little damage by UVC evaluated by MTT assay, cell growth curves and cell colony-forming assay, compared with that at the nadir of the expression of mPer2. Overexpression of mPER2, accompanied p53 upregulated, also demonstrated protective effect on NIH3T3 cells damaged by UVC. These results suggest that mPer2 plays a protective effect on cells damaged by UVC, whose mechanism may be involved in upregulated p53.

• 생명과학회지
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• 제7권3호
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• pp.205-211
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• 1997

수수에서 식물호르몬 에틸렌 생합성은 circadin 리듬 현상을 보인다고 이미 보고된바 있다. 따라서 본 실험은 또 다른 식물호르몬 지베렐린 생합성도 에틸렌과 같은 circadin 리듬 현상을 보이는지를 조사한 결과를 요약하면 다음과 같다. 일정기간 동안 12시간 주기의 밤과 낮 조건에서 생육시킨 식물체를 연속광조건으로 옮긴후 매 시간 마다 지베렐린의 함량변화를 조사하였다. 1. GA$_{12}$는 공시한 두 품종 모두에서 뚜렸한 circadin 리듬현상을 보였다. 2. GA$_{53}$과 GA$_{19}$는 일체의 리듬현상을 보이지 않았다. 3. GA$_{20}$과 GA$_{1}$은 circadin 리듬현상을 보였지만 연속광하에서 리듬의 정도는 12시간 주기의 정상적인 일장하에 비해 현저히 감소하였다. 4. 수수의 개화는 원적외선광의 조사에 의해 촉진됨에도 불구하고 이들 처리는 내생지베렐린의 함량을 변화시키지 않았다.

• Molecules and Cells
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• 제28권5호
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• pp.417-422
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• 2009

Mitogen activated protein kinase (MAPK) are known to get activated during various stress signals and transduce the message from the cell membrane to the nucleus for appropriate cellular reorganization. Though, a certain basal activity of MAPK is often observed in the control plants. Prolonged exposure of rice plants to lowered or elevated temperature exhibited a rhythm in the activation of MAPKs. We analyzed existence of a possible endogenous rhythm in the activity of MAPKs in rice plants. The plants growing at constant temperature entrained in 16/8 h day-night cycle showed diurnal rhythm in activity. When the activation of MAPK was tested under continuous conditions by shifting plants to continuous darkness for a period of 72 h, the periodic rhythm persisted and followed a circadian pattern. Analysis of the transcripts of group A, B and C members of MAPKs under above conditions by quantitative real time PCR revealed that the members of group C exhibit periodic rhythm. Our data indicates that the MAP kinase activity in rice follows rhythmic expression in a circadian manner.

• 한국동물학회:학술대회논문집
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• 한국동물학회 2000년도 한국생물과학협회 학술발표대회
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• pp.192.1-192
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• 2000

No Abstract, See Full Text

• 한국광과학회:학술대회논문집
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• 한국광과학회 2005년도 제12회 학술대회 논문초록
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• pp.55-55
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• 2005