Mariko Izumo

The University of Texas Southwestern Medical Center

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Joseph S. Takahashi

Howard Hughes Medical Institute

Collin J. Nadarajah

Washington University in St. Louis

Filipa Rijo‐Ferreira

Berkeley Public Health Division

Patrick W. Sheehan

Washington University in St. Louis

Victoria A. Acosta-Rodríguez

The University of Texas Southwestern Medical Center

Erik S. Musiek

Washington University in St. Louis

Carla B. Green

The University of Texas Southwestern Medical Center

Carl Hirschie Johnson

Vanderbilt University

Ben A. Barres

Stanford University

Brian V. Lananna

Washington University in St. Louis

Cooperative Institutions

The University of Texas Southwestern Medical Center

Washington University in St. Louis

Northwestern University

Howard Hughes Medical Institute

Hope Center for Neurological Disorders

University of Chicago

Southwestern Medical Center

Harvard University

The University of Texas at Dallas

Vanderbilt University

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Circadian gene expression in mammalian fibroblasts revealed by real-time luminescence reporting: Temperature compensation and damping

Proceedings of the National Academy of Sciences (2003)

Mariko Izumo Carl Hirschie Johnson Shin Yamazaki

Mammalian cells such as rat-1 fibroblasts have been shown to exhibit daily oscillations in the expression of several gene transcripts in culture. After induction, these oscillations persist with a period of ≈24 h for several days. This characteristic suggests that the oscillations are controlled by a circadian clock, but the crucial criterion of temperature compensation has not been demonstrated for rat-1 fibroblasts. We have developed an automated assay of circadian expression of the mPer1 promoter in rat-1 fibroblasts that have been stably transfected with a luciferase reporter. Using this cell culture-based in vitro luminescent reporter assay, we found that the daily oscillation of mPer1 promoter activity in rat-1 cells is temperature compensated over the range of 28.5-36.5°C. This finding means that these oscillations are bona fide circadian rhythms. Moreover, the circadian clock of these homeothermic mammalian cells not only is temperature compensated but also is overcompensated such that it runs faster at cooler temperatures (Q 10 of 0.85-0.88). The oscillations in rat-1 fibroblasts damp more rapidly at cooler temperatures, and damping is not due to cells becoming unhealthy because a second stimulus will reinitiate a robust rhythm. These data show that rat-1 cell cultures that are stably transfected with luminescence reporters are an excellent model system for studying circadian clocks at the cellular level in mammals.

Oscillation (cell signaling)

10.1073/pnas.2536313100

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Citations (148)

Hormonal Control of Root Hair Growth and Development

Springer eBooks (2000)

Masayuki Katsumi Mariko Izumo Robert W. Ridge

Root hair

Plant hormone

10.1007/978-4-431-68370-4_7

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Citations (12)

Selective Suppression of Local Circuits during Movement Preparation in the Mouse Motor Cortex

Cell Reports (2017)

Masashi Hasegawa Kei Majima Takahide Itokazu Takakuni Maki Urban-Raphael Albrecht

Prepared movements are more efficient than those that are not prepared for. Although changes in cortical activity have been observed prior to a forthcoming action, the circuits involved in motor preparation remain unclear. Here, we use in vivo two-photon calcium imaging to uncover changes in the motor cortex during variable waiting periods prior to a forepaw reaching task in mice. Consistent with previous reports, we observed a subset of neurons with increased activity during the waiting period; however, these neurons did not account for the degree of preparation as defined by reaction time (RT). Instead, the suppression of activity of distinct neurons in the same cortical area better accounts for RT. This suppression of neural activity resulted in a distinct and reproducible pattern when mice were well prepared. Thus, the selective suppression of network activity in the motor cortex may be a key feature of prepared movements.

Biological neural network

Calcium imaging

Premovement neuronal activity

Neural Activity

Cortical neurons

10.1016/j.celrep.2017.02.043

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Citations (39)

Misaligned feeding uncouples daily rhythms within brown adipose tissue and between peripheral clocks

Cell Reports (2024)

Victoria A. Acosta-Rodríguez Filipa Rijo‐Ferreira Laura van Rosmalen Mariko Izumo Noheon Park

10.1016/j.celrep.2024.114523

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Citations (1)

Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1

SSRN Electronic Journal (2018)

Brian V. Lananna Collin J. Nadarajah Mariko Izumo Michelle R. Cedeño David D. Xiong

Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults, and plays a critical role in brain health and disease. We report that the core clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism, and via a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation in vitro and in vivo, mediated in part by suppression of glutathione-s-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a novel mechanism by which the circadian clock could influence many aspects of brain function and neurologic disease.

10.2139/ssrn.3212831

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Citations (1)

Dual-Color Single-Cell Imaging of the Suprachiasmatic Nucleus Reveals a Circadian Role in Network Synchrony

Neuron (2020)

Yongli Shan John H. Abel Yan Li Mariko Izumo Kimberly H. Cox

10.1016/j.neuron.2020.07.012

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Citations (65)

Cycling of CRYPTOCHROME Proteins Is Not Necessary for Circadian-Clock Function in Mammalian Fibroblasts

Current Biology (2007)

Yunzhen Fan Akiko Hida Daniel A. Anderson Mariko Izumo Carl Hirschie Johnson

Clockwork

PER2

PER1

Oscillating gene

10.1016/j.cub.2007.05.048

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Citations (65)

Circadian Alignment of Feeding Regulates Lifespan Extension by Caloric Restriction

Innovation in Aging (2021)

Victoria A. Acosta-Rodríguez Filipa Rijo‐Ferreira Mariko Izumo Pin Xu Carla A. Green

Abstract Caloric restriction (CR) promotes longevity in several species. Classic CR protocols often lead to chronic cycles of 2h-feeding/22h-fasting, raising the question whether calories, fasting or time of day are causal. To address this, we tested an AL control group and five CR protocols with different timing and duration of feeding/fasting cycles. C57BL/6J male mice were subjected to 30% CR as one single meal a day at the beginning of the day or night (classical protocols with < 2h feeding, CR-day and CR-night), or smaller meals distributed for 12h (CR-day-12h and CR-night-12h), or evenly spread out throughout 24h (CR-spread) to abolish the otherwise daily feeding pattern adopted by nocturnal animals. We found that CR alone is sufficient to extend lifespan without fasting. However, the benefits are enhanced if feeding/fasting cycles are present and match their normal nocturnal activity. Circadian alignment of feeding with at least 12h fasting boosts CR-mediated increase on survival in mice, independently body weight. Aging leads to widespread upregulation of inflammation-related genes and downregulation of metabolic pathways in liver from ad lib fed mice; whereas CR at night ameliorates these aging-related changes and preserves circadian oscillations in gene expression. Overall, our results demonstrate that circadian interventions promote longevity and provide a novel perspective for elucidating mechanisms of aging.

Caloric theory

Calorie

Intermittent Fasting

Calorie Restriction

Restricted diet

10.1093/geroni/igab046.442

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Citations (0)

Cell-Autonomous Regulation of Astrocyte Activation by the Circadian Clock Protein BMAL1

Cell Reports (2018)

Brian V. Lananna Collin J. Nadarajah Mariko Izumo Michelle R. Cedeño David D. Xiong

Circadian clock dysfunction is a common symptom of aging and neurodegenerative diseases, though its impact on brain health is poorly understood. Astrocyte activation occurs in response to diverse insults and plays a critical role in brain health and disease. We report that the core circadian clock protein BMAL1 regulates astrogliosis in a synergistic manner via a cell-autonomous mechanism and a lesser non-cell-autonomous signal from neurons. Astrocyte-specific Bmal1 deletion induces astrocyte activation and inflammatory gene expression in vitro and in vivo, mediated in part by suppression of glutathione-S-transferase signaling. Functionally, loss of Bmal1 in astrocytes promotes neuronal death in vitro. Our results demonstrate that the core clock protein BMAL1 regulates astrocyte activation and function in vivo, elucidating a mechanism by which the circadian clock could influence many aspects of brain function and neurological disease.

Astrogliosis

10.1016/j.celrep.2018.09.015

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Citations (124)

Neuromedin S-Producing Neurons Act as Essential Pacemakers in the Suprachiasmatic Nucleus to Couple Clock Neurons and Dictate Circadian Rhythms

Neuron (2015)

Ivan T. Lee Alexander S. Chang Manabu Manandhar Yongli Shan Junmei Fan

Premovement neuronal activity

10.1016/j.neuron.2015.02.006

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Citations (163)