The Experts below are selected from a list of 4122 Experts worldwide ranked by ideXlab platform
Dick F. Swaab - One of the best experts on this subject based on the ideXlab platform.
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Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer’s disease
Sleep Medicine, 2007Co-Authors: Dick F. SwaabAbstract:Circadian rhythm disturbances, such as sleep disorders, are frequently seen in aging and are even more pronounced in Alzheimer's disease (AD). Alterations in the biological clock, the suprachiasmatic nucleus (SCN), and the pineal gland during aging and AD are considered to be the biological basis for these circadian rhythm disturbances. Recently, our group found that pineal melatonin secretion and pineal clock Gene Oscillation were disrupted in AD patients, and surprisingly even in non-demented controls with the earliest signs of AD neuropathology (neuropathological Braak stages I-II), in contrast to non-demented controls without AD neuropathology. Furthermore, a functional disruption of the SCN was observed from the earliest AD stages onwards, as shown by decreased vasopressin mRNA, a clock-controlled major output of the SCN. The observed functional disconnection between the SCN and the pineal from the earliest AD stage onwards seems to account for the pineal clock Gene and melatonin changes and underlies circadian rhythm disturbances in AD. This paper further discusses potential therapeutic strategies for reactivation of the circadian timing system, including melatonin and bright light therapy. As the presence of melatonin MT1 receptor in the SCN is extremely decreased in late AD patients, supplementary melatonin in the late AD stages may not lead to clear effects on circadian rhythm disorders.
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pineal clock Gene Oscillation is disturbed in alzheimer s disease due to functional disconnection from the master clock
The FASEB Journal, 2006Co-Authors: David F. Fischer, Andries Kalsbeek, Jan Van Der Vliet, Caroline Van Heijningen, Rongyu Liu, Jiang-ning Zhou, Marielaure Garidouboof, Dick F. SwaabAbstract:The suprachiasmatic nucleus (SCN) is the "master clock" of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease (AD). Here we show that the clock Genes hBmal1, hCry1, and hPer1 were rhythmically expressed in the pineal of controls (Braak 0). Moreover, hPer1 and hbeta1-adrenergic receptor (hbeta1-ADR) mRNA were positively correlated and showed a similar daily pattern. In contrast, in both preclinical (Braak I-II) and clinical AD patients (Braak V-VI), the rhythmic expression of clock Genes was lost as well as the correlation between hPer1 and hbeta1-ADR mRNA. Intriguingly, hCry1 mRNA was increased in clinical AD. These changes are probably due to a disruption of the SCN control, as they were mirrored in the rat pineal deprived of SCN control. Indeed, a functional disruption of the SCN was observed from the earliest AD stages onward, as shown by decreased vasopressin mRNA, a clock-controlled major output of the SCN. Thus, a functional disconnection between the SCN and the pineal from the earliest AD stage onward could account for the pineal clock Gene changes and underlie the circadian rhythm disturbances in AD.
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pineal clock Gene Oscillation is disturbed in alzheimer s disease due to functional disconnection from the master clock
The FASEB Journal, 2006Co-Authors: Yinghui Wu, David F. Fischer, Andries Kalsbeek, Jiang-ning Zhou, Marielaure Garidouboof, Jan Van Der Vliet, Caroline Van Heijningen, Dick F. SwaabAbstract:The suprachiasmatic nucleus (SCN) is the “master clock” of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer’s disease (AD). Here we show that the clock Genes hBmal1, hCry1, and hPer1 were rhythmically expressed in the pineal of controls (Braak 0). Moreover, hPer1 and hβ1-adrenergic receptor (hβ1-ADR) mRNA were positively correlated and showed a similar daily pattern. In contrast, in both preclinical (Braak I-II) and clinical AD patients (Braak V-VI), the rhythmic expression of clock Genes was lost as well as the correlation between hPer1 and hβ1-ADR mRNA. Intriguingly, hCry1 mRNA was increased in clinical AD. These changes are probably due to a disruption of the SCN control, as they were mirrored in the rat pineal deprived of SCN control. Indeed, a functional disruption of the SCN was observed from the earliest AD stages onward, ...
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Pineal clock Gene Oscillation is disturbed in Alzheimer’s disease, due to functional disconnection from the “master clock”
The FASEB Journal, 2006Co-Authors: David F. Fischer, Andries Kalsbeek, Marie-laure Garidou-boof, Jan Van Der Vliet, Caroline Van Heijningen, Rongyu Liu, Jiang-ning Zhou, Dick F. SwaabAbstract:The suprachiasmatic nucleus (SCN) is the "master clock" of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease (AD). Here we show that the clock Genes hBmal1, hCry1, and hPer1 were rhythmically expressed in the pineal of controls (Braak 0). Moreover, hPer1 and hbeta1-adrenergic receptor (hbeta1-ADR) mRNA were positively correlated and showed a similar daily pattern. In contrast, in both preclinical (Braak I-II) and clinical AD patients (Braak V-VI), the rhythmic expression of clock Genes was lost as well as the correlation between hPer1 and hbeta1-ADR mRNA. Intriguingly, hCry1 mRNA was increased in clinical AD. These changes are probably due to a disruption of the SCN control, as they were mirrored in the rat pineal deprived of SCN control. Indeed, a functional disruption of the SCN was observed from the earliest AD stages onward, as shown by decreased vasopressin mRNA, a clock-controlled major output of the SCN. Thus, a functional disconnection between the SCN and the pineal from the earliest AD stage onward could account for the pineal clock Gene changes and underlie the circadian rhythm disturbances in AD.
Han Kyoung Choe - One of the best experts on this subject based on the ideXlab platform.
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microRNA-25 as a novel modulator of circadian Period2 Gene Oscillation.
Experimental and Molecular Medicine, 2020Co-Authors: Inah Park, Han Kyoung Choe, Doyeon Kim, Jeongah Kim, Sangwon Jang, Mijung Choi, Youngshik Choe, Kyungjin KimAbstract:Circadian clock controls an organism's biological rhythm and regulates its physiological processes in response to external time cues. Most living organisms have their own time-keeping mechanism that is maintained by transcriptional-translational autoregulatory feedback loops involving several core clock Genes, such as Period. Recent studies have found the relevance between the modulation of circadian Oscillation and posttranscriptional modifications by microRNAs (miRNAs). However, there are limited studies on candidate miRNAs that regulate circadian Oscillation. Here, we characterize the functions of novel miRNA-25 regulating circadian Period2 (Per2) expression. Using several in silico algorithms, we identified novel miR-25-3p that, together with miR-24-3p, targets the Per2 Gene. Luciferase reporter assays validated that miR-25-3p and miR-24-3p repressed Per2 expression and confirmed their predicted binding sites in the 3'-untranslated region (UTR) of Per2 mRNA. Real-time bioluminescence analyses using Per2::Luc mouse embryonic fibroblasts confirmed that PER2 protein Oscillation patterns were responsive to miR-25-3p and miR-24-3. The overexpression of miR-25-3p or miR-24-3p resulted in the dampening and period shortening of the PER2::LUC Oscillation, while inhibition of either miRNA increased the relative amplitude of the PER2::LUC Oscillation. Notably, endogenous miR-25-3p expression in the suprachiasmatic nucleus (SCN) showed no circadian rhythmicity, but the expression levels differed in various brain regions and peripheral tissues. These results suggest that the posttranscriptional regulation of miR-25-3p and miR-24-3p may differ according to Per2 Gene expression in different tissue regions. In summary, we found that novel miR-25-3p was involved in fine-tuning circadian rhythmicity by regulating Per2 Oscillation at the posttranscriptional level and that it functioned synergistically with miR-24-3p to affect Per2 Oscillation.
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microRNA-25 as a novel modulator of circadian Period2 Gene Oscillation
Experimental & Molecular Medicine, 2020Co-Authors: Inah Park, Han Kyoung Choe, Sangwon Jang, Mijung Choi, Youngshik ChoeAbstract:Circadian clock controls an organism’s biological rhythm and regulates its physiological processes in response to external time cues. Most living organisms have their own time-keeping mechanism that is maintained by transcriptional–translational autoregulatory feedback loops involving several core clock Genes, such as Period . Recent studies have found the relevance between the modulation of circadian Oscillation and posttranscriptional modifications by microRNAs (miRNAs). However, there are limited studies on candidate miRNAs that regulate circadian Oscillation. Here, we characterize the functions of novel miRNA-25 regulating circadian Period2 ( Per2 ) expression. Using several in silico algorithms, we identified novel miR-25-3p that, together with miR-24-3p, targets the Per2 Gene. Luciferase reporter assays validated that miR-25-3p and miR-24-3p repressed Per2 expression and confirmed their predicted binding sites in the 3′-untranslated region (UTR) of Per2 mRNA. Real-time bioluminescence analyses using Per2::Luc mouse embryonic fibroblasts confirmed that PER2 protein Oscillation patterns were responsive to miR-25-3p and miR-24-3. The overexpression of miR-25-3p or miR-24-3p resulted in the dampening and period shortening of the PER2::LUC Oscillation, while inhibition of either miRNA increased the relative amplitude of the PER2::LUC Oscillation. Notably, endogenous miR-25-3p expression in the suprachiasmatic nucleus (SCN) showed no circadian rhythmicity, but the expression levels differed in various brain regions and peripheral tissues. These results suggest that the posttranscriptional regulation of miR-25-3p and miR-24-3p may differ according to Per2 Gene expression in different tissue regions. In summary, we found that novel miR-25-3p was involved in fine-tuning circadian rhythmicity by regulating Per2 Oscillation at the posttranscriptional level and that it functioned synergistically with miR-24-3p to affect Per2 Oscillation. A newly identified microRNA plays a key role in fine-tuning the Genetic interactions governing the circadian rhythms in mammals, according to researchers in South Korea. Numerous studies have suggested that the Period Genes, which negatively regulate the CLOCK and BMAL1 Genes to produce a 24-hour feedback loop, may be further modified by microRNAs after they are transcribed. Kyungjin Kim at Daegu Gyeongbuk Institute of Science and Technology, South Korea, and co-workers confirmed that a novel microRNA, miR-25-3p, reduces the expression of a Period Gene, Per2 , in mice. When miR-25-3p is over-expressed, it dampens and shortens the Oscillations of Per2 levels. Interestingly, the researchers showed that natural miR-25-3p expression levels varied across different parts of the brain, supporting the theory that different tissues of the body maintain their own unique circadian cycles.
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Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus
Academya Publishing Co., 2015Co-Authors: Jinmi Koo, Han Kyoung Choe, Hee-dae Kim, Sung Kook Chun, Gi Hoon Son, Kyungjin KimAbstract:BackgroundIn 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.MethodsWe 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.ResultsAdministration 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.ConclusionThese 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
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Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo
Endocrinology and Metabolism, 2015Co-Authors: Jinmi Koo, Han Kyoung Choe, Hee-dae Kim, Sung Kook Chun, Gi Hoon Son, Kyungjin KimAbstract: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.
Youngshik Choe - One of the best experts on this subject based on the ideXlab platform.
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microRNA-25 as a novel modulator of circadian Period2 Gene Oscillation.
Experimental and Molecular Medicine, 2020Co-Authors: Inah Park, Han Kyoung Choe, Doyeon Kim, Jeongah Kim, Sangwon Jang, Mijung Choi, Youngshik Choe, Kyungjin KimAbstract:Circadian clock controls an organism's biological rhythm and regulates its physiological processes in response to external time cues. Most living organisms have their own time-keeping mechanism that is maintained by transcriptional-translational autoregulatory feedback loops involving several core clock Genes, such as Period. Recent studies have found the relevance between the modulation of circadian Oscillation and posttranscriptional modifications by microRNAs (miRNAs). However, there are limited studies on candidate miRNAs that regulate circadian Oscillation. Here, we characterize the functions of novel miRNA-25 regulating circadian Period2 (Per2) expression. Using several in silico algorithms, we identified novel miR-25-3p that, together with miR-24-3p, targets the Per2 Gene. Luciferase reporter assays validated that miR-25-3p and miR-24-3p repressed Per2 expression and confirmed their predicted binding sites in the 3'-untranslated region (UTR) of Per2 mRNA. Real-time bioluminescence analyses using Per2::Luc mouse embryonic fibroblasts confirmed that PER2 protein Oscillation patterns were responsive to miR-25-3p and miR-24-3. The overexpression of miR-25-3p or miR-24-3p resulted in the dampening and period shortening of the PER2::LUC Oscillation, while inhibition of either miRNA increased the relative amplitude of the PER2::LUC Oscillation. Notably, endogenous miR-25-3p expression in the suprachiasmatic nucleus (SCN) showed no circadian rhythmicity, but the expression levels differed in various brain regions and peripheral tissues. These results suggest that the posttranscriptional regulation of miR-25-3p and miR-24-3p may differ according to Per2 Gene expression in different tissue regions. In summary, we found that novel miR-25-3p was involved in fine-tuning circadian rhythmicity by regulating Per2 Oscillation at the posttranscriptional level and that it functioned synergistically with miR-24-3p to affect Per2 Oscillation.
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microRNA-25 as a novel modulator of circadian Period2 Gene Oscillation
Experimental & Molecular Medicine, 2020Co-Authors: Inah Park, Han Kyoung Choe, Sangwon Jang, Mijung Choi, Youngshik ChoeAbstract:Circadian clock controls an organism’s biological rhythm and regulates its physiological processes in response to external time cues. Most living organisms have their own time-keeping mechanism that is maintained by transcriptional–translational autoregulatory feedback loops involving several core clock Genes, such as Period . Recent studies have found the relevance between the modulation of circadian Oscillation and posttranscriptional modifications by microRNAs (miRNAs). However, there are limited studies on candidate miRNAs that regulate circadian Oscillation. Here, we characterize the functions of novel miRNA-25 regulating circadian Period2 ( Per2 ) expression. Using several in silico algorithms, we identified novel miR-25-3p that, together with miR-24-3p, targets the Per2 Gene. Luciferase reporter assays validated that miR-25-3p and miR-24-3p repressed Per2 expression and confirmed their predicted binding sites in the 3′-untranslated region (UTR) of Per2 mRNA. Real-time bioluminescence analyses using Per2::Luc mouse embryonic fibroblasts confirmed that PER2 protein Oscillation patterns were responsive to miR-25-3p and miR-24-3. The overexpression of miR-25-3p or miR-24-3p resulted in the dampening and period shortening of the PER2::LUC Oscillation, while inhibition of either miRNA increased the relative amplitude of the PER2::LUC Oscillation. Notably, endogenous miR-25-3p expression in the suprachiasmatic nucleus (SCN) showed no circadian rhythmicity, but the expression levels differed in various brain regions and peripheral tissues. These results suggest that the posttranscriptional regulation of miR-25-3p and miR-24-3p may differ according to Per2 Gene expression in different tissue regions. In summary, we found that novel miR-25-3p was involved in fine-tuning circadian rhythmicity by regulating Per2 Oscillation at the posttranscriptional level and that it functioned synergistically with miR-24-3p to affect Per2 Oscillation. A newly identified microRNA plays a key role in fine-tuning the Genetic interactions governing the circadian rhythms in mammals, according to researchers in South Korea. Numerous studies have suggested that the Period Genes, which negatively regulate the CLOCK and BMAL1 Genes to produce a 24-hour feedback loop, may be further modified by microRNAs after they are transcribed. Kyungjin Kim at Daegu Gyeongbuk Institute of Science and Technology, South Korea, and co-workers confirmed that a novel microRNA, miR-25-3p, reduces the expression of a Period Gene, Per2 , in mice. When miR-25-3p is over-expressed, it dampens and shortens the Oscillations of Per2 levels. Interestingly, the researchers showed that natural miR-25-3p expression levels varied across different parts of the brain, supporting the theory that different tissues of the body maintain their own unique circadian cycles.
David F. Fischer - One of the best experts on this subject based on the ideXlab platform.
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pineal clock Gene Oscillation is disturbed in alzheimer s disease due to functional disconnection from the master clock
The FASEB Journal, 2006Co-Authors: David F. Fischer, Andries Kalsbeek, Jan Van Der Vliet, Caroline Van Heijningen, Rongyu Liu, Jiang-ning Zhou, Marielaure Garidouboof, Dick F. SwaabAbstract:The suprachiasmatic nucleus (SCN) is the "master clock" of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease (AD). Here we show that the clock Genes hBmal1, hCry1, and hPer1 were rhythmically expressed in the pineal of controls (Braak 0). Moreover, hPer1 and hbeta1-adrenergic receptor (hbeta1-ADR) mRNA were positively correlated and showed a similar daily pattern. In contrast, in both preclinical (Braak I-II) and clinical AD patients (Braak V-VI), the rhythmic expression of clock Genes was lost as well as the correlation between hPer1 and hbeta1-ADR mRNA. Intriguingly, hCry1 mRNA was increased in clinical AD. These changes are probably due to a disruption of the SCN control, as they were mirrored in the rat pineal deprived of SCN control. Indeed, a functional disruption of the SCN was observed from the earliest AD stages onward, as shown by decreased vasopressin mRNA, a clock-controlled major output of the SCN. Thus, a functional disconnection between the SCN and the pineal from the earliest AD stage onward could account for the pineal clock Gene changes and underlie the circadian rhythm disturbances in AD.
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pineal clock Gene Oscillation is disturbed in alzheimer s disease due to functional disconnection from the master clock
The FASEB Journal, 2006Co-Authors: Yinghui Wu, David F. Fischer, Andries Kalsbeek, Jiang-ning Zhou, Marielaure Garidouboof, Jan Van Der Vliet, Caroline Van Heijningen, Dick F. SwaabAbstract:The suprachiasmatic nucleus (SCN) is the “master clock” of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer’s disease (AD). Here we show that the clock Genes hBmal1, hCry1, and hPer1 were rhythmically expressed in the pineal of controls (Braak 0). Moreover, hPer1 and hβ1-adrenergic receptor (hβ1-ADR) mRNA were positively correlated and showed a similar daily pattern. In contrast, in both preclinical (Braak I-II) and clinical AD patients (Braak V-VI), the rhythmic expression of clock Genes was lost as well as the correlation between hPer1 and hβ1-ADR mRNA. Intriguingly, hCry1 mRNA was increased in clinical AD. These changes are probably due to a disruption of the SCN control, as they were mirrored in the rat pineal deprived of SCN control. Indeed, a functional disruption of the SCN was observed from the earliest AD stages onward, ...
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Pineal clock Gene Oscillation is disturbed in Alzheimer’s disease, due to functional disconnection from the “master clock”
The FASEB Journal, 2006Co-Authors: David F. Fischer, Andries Kalsbeek, Marie-laure Garidou-boof, Jan Van Der Vliet, Caroline Van Heijningen, Rongyu Liu, Jiang-ning Zhou, Dick F. SwaabAbstract:The suprachiasmatic nucleus (SCN) is the "master clock" of the mammalian brain. It coordinates the peripheral clocks in the body, including the pineal clock that receives SCN input via a multisynaptic noradrenergic pathway. Rhythmic pineal melatonin production is disrupted in Alzheimer's disease (AD). Here we show that the clock Genes hBmal1, hCry1, and hPer1 were rhythmically expressed in the pineal of controls (Braak 0). Moreover, hPer1 and hbeta1-adrenergic receptor (hbeta1-ADR) mRNA were positively correlated and showed a similar daily pattern. In contrast, in both preclinical (Braak I-II) and clinical AD patients (Braak V-VI), the rhythmic expression of clock Genes was lost as well as the correlation between hPer1 and hbeta1-ADR mRNA. Intriguingly, hCry1 mRNA was increased in clinical AD. These changes are probably due to a disruption of the SCN control, as they were mirrored in the rat pineal deprived of SCN control. Indeed, a functional disruption of the SCN was observed from the earliest AD stages onward, as shown by decreased vasopressin mRNA, a clock-controlled major output of the SCN. Thus, a functional disconnection between the SCN and the pineal from the earliest AD stage onward could account for the pineal clock Gene changes and underlie the circadian rhythm disturbances in AD.
Kyungjin Kim - One of the best experts on this subject based on the ideXlab platform.
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microRNA-25 as a novel modulator of circadian Period2 Gene Oscillation.
Experimental and Molecular Medicine, 2020Co-Authors: Inah Park, Han Kyoung Choe, Doyeon Kim, Jeongah Kim, Sangwon Jang, Mijung Choi, Youngshik Choe, Kyungjin KimAbstract:Circadian clock controls an organism's biological rhythm and regulates its physiological processes in response to external time cues. Most living organisms have their own time-keeping mechanism that is maintained by transcriptional-translational autoregulatory feedback loops involving several core clock Genes, such as Period. Recent studies have found the relevance between the modulation of circadian Oscillation and posttranscriptional modifications by microRNAs (miRNAs). However, there are limited studies on candidate miRNAs that regulate circadian Oscillation. Here, we characterize the functions of novel miRNA-25 regulating circadian Period2 (Per2) expression. Using several in silico algorithms, we identified novel miR-25-3p that, together with miR-24-3p, targets the Per2 Gene. Luciferase reporter assays validated that miR-25-3p and miR-24-3p repressed Per2 expression and confirmed their predicted binding sites in the 3'-untranslated region (UTR) of Per2 mRNA. Real-time bioluminescence analyses using Per2::Luc mouse embryonic fibroblasts confirmed that PER2 protein Oscillation patterns were responsive to miR-25-3p and miR-24-3. The overexpression of miR-25-3p or miR-24-3p resulted in the dampening and period shortening of the PER2::LUC Oscillation, while inhibition of either miRNA increased the relative amplitude of the PER2::LUC Oscillation. Notably, endogenous miR-25-3p expression in the suprachiasmatic nucleus (SCN) showed no circadian rhythmicity, but the expression levels differed in various brain regions and peripheral tissues. These results suggest that the posttranscriptional regulation of miR-25-3p and miR-24-3p may differ according to Per2 Gene expression in different tissue regions. In summary, we found that novel miR-25-3p was involved in fine-tuning circadian rhythmicity by regulating Per2 Oscillation at the posttranscriptional level and that it functioned synergistically with miR-24-3p to affect Per2 Oscillation.
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Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus
Academya Publishing Co., 2015Co-Authors: Jinmi Koo, Han Kyoung Choe, Hee-dae Kim, Sung Kook Chun, Gi Hoon Son, Kyungjin KimAbstract:BackgroundIn 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.MethodsWe 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.ResultsAdministration 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.ConclusionThese 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
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Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo
Endocrinology and Metabolism, 2015Co-Authors: Jinmi Koo, Han Kyoung Choe, Hee-dae Kim, Sung Kook Chun, Gi Hoon Son, Kyungjin KimAbstract: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.