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      • KCI등재후보

        Mammalian Molecular Clocks

        권일민,최한경,손기훈,김경진 한국뇌신경과학회 2011 Experimental Neurobiology Vol.20 No.1

        As a consequence of the Earth's rotation, almost all organisms experience day and night cycles within a 24-hr period. To adapt and synchronize biological rhythms to external daily cycles, organisms have evolved an internal time-keeping system. In mammals, the master circadian pacemaker residing in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus generates circadian rhythmicity and orchestrates numerous subsidiary local clocks in other regions of the brain and peripheral tissues. Regardless of their locations, these circadian clocks are cell-autonomous and self- sustainable, implicating rhythmic oscillations in a variety of biochemical and metabolic processes. A group of core clock genes provides interlocking molecular feedback loops that drive the circadian rhythm even at the single-cell level. In addition to the core transcription/translation feedback loops, post-translational modifications also contribute to the fine regulation of molecular circadian clocks. In this article, we briefly review the molecular mechanisms and post-translational modifications of mammalian circadian clock regulation. We also discuss the organization of and communication between central and peripheral circadian oscillators of the mammalian circadian clock.

      • KCI등재

        Core clock gene, Bmal1, is required for optimal second-level interval production

        김윤경,최한경 한국통합생물학회 2023 Animal cells and systems Vol.27 No.1

        Perception and production of second-level temporal intervals are critical in several behavioral andcognitive processes, including adaptive anticipation, motor control, and social communication. These processes are impaired in several neurological and psychological disorders, such asParkinson’s disease and attention-deficit hyperactivity disorder. Although evidence indicatesthat second-level interval timing exhibit circadian patterns, it remains unclear whether the coreclock machinery controls the circadian pattern of interval timing. To investigate the role of coreclock molecules in interval timing capacity, we devised a behavioral assay called the intervaltiming task to examine prospective motor interval timing ability. In this task, the mouseproduces two separate nose pokes in a pretrained second-level interval to obtain a sucrosesolution as a reward. We discovered that interval perception in wild-type mice displayed acircadian pattern, with the best performance observed during the late active phase. Toinvestigate whether the core molecular clock is involved in the circadian control of intervaltiming, we employed Bmal1 knockout mice (BKO) in the interval timing task. The intervalproduction of BKO did not display any difference between early and late active phase, withoutreaching the optimal interval production level observed in wild-type. In summary, we reportthat the core clock gene Bmal1 is required for the optimal performance of prospective motortiming typically observed during the late part of the active period.

      • KCI등재

        Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo

        구진미,최한경,김희대,전성국,손기훈,김경진 대한내분비학회 2015 Endocrinology and metabolism Vol.30 No.3

        Background: In mammals, the master circadian pacemaker is localized in an area of the ventral hypothalamus known as the suprachiasmatic nucleus (SCN). Previous studies have shown that pacemaker neurons in the SCN are highly coupled to one another, and this coupling is crucial for intrinsic self-sustainability of the SCN central clock, which is distinguished from peripheral oscillators. One plausible mechanism underlying the intercellular communication may involve direct electrical connections mediated by gap junctions. Methods: We examined the effect of mefloquine, a neuronal gap junction blocker, on circadian Period 2 (Per2) gene oscillation in SCN slice cultures prepared from Per2::luciferase (PER2::LUC) knock-in mice using a real-time bioluminescence measurement system. Results: Administration of mefloquine causes instability in the pulse period and a slight reduction of amplitude in cyclic PER2::LUC expression. Blockade of gap junctions uncouples PER2::LUC-expressing cells, in terms of phase transition, which weakens synchrony among individual cellular rhythms. Conclusion: These findings suggest that neuronal gap junctions play an important role in synchronizing the central pacemaker neurons and contribute to the distinct self-sustainability of the SCN master clock.

      • KCI등재

        Implications of Circadian Rhythm in Dopamine and Mood Regulation

        김정아,장상원,최한경,정수영,손기훈,김경진 한국분자세포생물학회 2017 Molecules and cells Vol.40 No.7

        Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-erbα induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson’s disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

      • PC 통신서비스간의 상호접속 유인 연구

        안병훈,박용삼,최한경 에스케이텔레콤 (주) 1999 Telecommunications Review Vol.9 No.4

        본 논문에서는 그동안 국제 및 시내통신 서비스의 경우를 중심으로 진행되어 왔던 필수설비(essential facility) 보유기업간의 양방향 상호접속(two-way interconnection)에 관한 논의를 PC 통신서비스의 경우로 확장한다. 이로부터 개별 PC 통신사업자들은 망외부성(network externality) 극대화를 위해 자발적으로 상호접속할 유인을 갖음을 보인다. 또한 경쟁적PC 통신사업자간 서비스 대체성과 가입자 규모의 차이에 따라 상호접속이 용이할 수도, 그렇지 않을 수도 있게 되며 경우에따라서는 접속료 설정과 관련하여 반경쟁적 담합행위가 발생할 수 있음을 보인다. 마지막으로 분석결과를 현실의 사례에 적용해서 우리나라 4대 PC 통신업체간 상호접속의 가능성에 대해 고찰한다.

      • KCI등재

        Programming effects of maternal stress on the circadian system of adult offspring

        Seongsik Yun,이은정,최한경,Gi Hoon Son,Kyungjin Kim,정수영 생화학분자생물학회 2020 Experimental and molecular medicine Vol.52 No.-

        Maternal stress has long-lasting influences on the brain functions of offspring, and several brain regions have been proposed to mediate such programming. Although perinatal programming of crosstalk between the circadian and stress systems has been proposed, the functional consequences of prenatal stress on the circadian system and the underlying mechanisms remain largely unknown. Therefore, we investigated whether exposing pregnant mice to chronic restraint stress had prolonged effects on the suprachiasmatic nucleus (SCN), which bears the central pacemaker for mammalian circadian rhythms, of offspring. SCN explants from maternally stressed mice exhibited altered cyclic expression patterns of a luciferase reporter under control of the mouse Per1 promoter (mPer1::LUC), which manifested as a decreased amplitude and impaired stability of the rhythm. Bioluminescence imaging at the single-cell level subsequently revealed that impaired synchrony among individual cells was responsible for the impaired rhythmicity. These intrinsic defects appeared to persist during adulthood. Adult male offspring from stressed mothers showed advanced-phase behavioral rhythms with impaired stability as well as altered clock gene expression in the SCN. In addition to affecting the central rhythm, maternal stress also had prolonged influences on the circadian characteristics of the adrenal gland and liver, as determined by circulating corticosterone levels and hepatic glycogen content, and on canonical clock gene mRNA expression in those tissues. Taken together, our findings suggest that the SCN is a key target of the programming effects of maternal stress. The widespread effects of circadian disruptions caused by a misprogrammed clock may have further impacts on metabolic and mental health in later life.

      • KCI등재

        Effects of Intermittent Fasting on the Circulating Levels and Circadian Rhythms of Hormones

        김보혜,주예나,김민선,최한경,Qingchun Tong,권오빈 대한내분비학회 2021 Endocrinology and metabolism Vol.36 No.4

        Intermittent fasting has become an increasingly popular strategy in losing weight and associated reduction in obesity-related medicalcomplications. Overwhelming studies support metabolic improvements from intermittent fasting in blood glucose levels, cardiac andbrain function, and other health benefits, in addition to weight loss. However, concerns have also been raised on side effects including muscle loss, ketosis, and electrolyte imbalance. Of particular concern, the effect of intermittent fasting on hormonal circadianrhythms has received little attention. Given the known importance of circadian hormonal changes to normal physiology, potentialdetrimental effects by dysregulation of hormonal changes deserve careful discussions. In this review, we describe the changes in circadian rhythms of hormones caused by intermittent fasting. We covered major hormones commonly pathophysiologically involvedin clinical endocrinology, including insulin, thyroid hormones, and glucocorticoids. Given that intermittent fasting could alter boththe level and frequency of hormone secretion, decisions on practicing intermittent fasting should take more considerations on potential detrimental consequences versus beneficial effects pertaining to individual health conditions.

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