Faculty Profiles - YAMAGUCHI Yoshiaki

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YAMAGUCHI Yoshiaki

Organization

Faculty of Chemistry, Materials and Bioengineering Associate Professor

Profile

概日時計の中枢である視交叉上核が担う生理機能を、分子のレベルから研究しています。

External link

Degree

Ph.D ( 2004.3 Kyoto University )

Research Interests

生物時計
組織特異的ノックアウト
神経細胞不活性化
マウス
リズム異常
組織特異的Cre
遺伝子改変マウス
リズム同調
Per
グルタミン酸受容体
バソプレッシン
神経機能抑制
時差
概日時計
発光
遺伝子
生理学
脳科学
皮膚
発現制御
AMPA受容体
神経生理学
包括脳ネットワーク
高血圧
臓器の時計
Molecular Neurobiology
Neurophysiology
分子神経生物学
アデノ随伴ウイルス
体内時計
アラトスタチン
サーカディアンリズム
時計遺伝子
概日リズム
視交叉上核

Research Areas

Life Science / Animal physiological chemistry, physiology and behavioral biology / Circadian rhythm
Life Science / Neuroscience-general
Life Science / Pharmaceutical hygiene and biochemistry
Life Science / Basic brain sciences

Education

京都大学大学院生命科学研究科高次生命科学専攻博士後期課程

2001.4 - 2004.3

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京都大学大学院生命科学研究科高次生命科学専攻修士課程

1999.4 - 2001.3

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Country： Japan

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Kyoto University Faculty of Pharmaceutical Sciences

1995.4 - 1999.3

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Country： Japan

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Research History

Kansai University Faculty of Chemistry , Materials and Bioengineering Department of Life Science and Biotechnology

2023.4

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京都大学大学院薬学研究科講師

2018.8 - 2023.3

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京都大学大学院薬学研究科助教

2007.11 - 2018.7

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Assitant Professor (Kyoto University)

2007.11 - 2018.7

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Research Associate (Salk Institute, CA, USA)

2006 - 2007

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リサーチアソシエイト（米国ソーク研究所）

2004.4 - 2007.10

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日本学術振興会海外特別研究員（米国ソーク研究所）

2004.4 - 2006.3

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JSPS Postdoctral Fellowship for Research Abroad (Salk Institute, CA, USA)

2004 - 2006

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日本学術振興会特別研究員DC1（京都大学生命科学研究科）

2001.4 - 2004.3

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JSPS Research Fellowship for Young Scientists DC1 (Kyoto University)

2001 - 2004

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Professional Memberships

The Japan Endocrine Society

2019.4 - Present

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Japan Neuroendocrine Society

2014.4 - Present

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THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

2012.3 - Present

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THE JAPANESE BIOCHEMICAL SOCIETY

2012.3 - Present

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JAPANESE SOCIETY FOR CHRONOBIOLOGY

2009.6 - Present

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THE PHARMACEUTICAL SOCIETY OF JAPAN

2009.2 - Present

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The Japan Neuroscience Society

2006.6 - Present

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Society for Neuroscience

2002.3 - Present

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Papers

Somatostatin regulates the clock sensitivity to evening light. International journal

Yoshiaki Yamaguchi, Satoru Masubuchi, Emi Kiyokage, Kazunori Toida, Yasutaka Mizoro, Toru Suzuki, Miho Sato, Jean-Michel Fustin, Keiko Tominaga, Hitoshi Okamura

Scientific reports 15 ( 1 ) 42664 - 42664 2025.11

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Language：English Publishing type：Research paper (scientific journal)

Entrainment of the internal clock to the light-dark cycle is a fundamental feature of biological rhythms. Here, we show that animals genetically deficient for somatostatin (SST) are unable to respond normally to long photoperiodic conditions, showing a significantly delayed phase of activity. The phase delay is also reproduced in the cognate SSTR1 receptor knockout mice and in mice in which SSTR1 is pharmacologically inhibited. We also provide histological evidence that SST inhibits light-induced activation of SSTR1 cells. Furthermore, chronic administration of CH-275, an SSTR1 agonist, normalizes the phase delay of the circadian clock in SST-deficient mice under long photoperiod. Together, these results provide insights into the inhibitory effect of the SST-SSTR1 system in the regulation of light sensitivity of the central clock in the SCN at dusk.

DOI： 10.1038/s41598-025-26904-2

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An intact pituitary vasopressin system is critical for building a robust circadian clock in the suprachiasmatic nucleus. International journal

Yoshiaki Yamaguchi, Yota Maekawa, Kyohei Kabashima, Takanobu Mizuno, Motomi Tainaka, Toru Suzuki, Kumiko Dojo, Takeichiro Tominaga, Sayaka Kuroiwa, Satoru Masubuchi, Masao Doi, Keiko Tominaga, Kazuto Kobayashi, Satoshi Yamagata, Keiichi Itoi, Manabu Abe, William J Schwartz, Kenji Sakimura, Hitoshi Okamura

Proceedings of the National Academy of Sciences of the United States of America 120 ( 43 ) e2308489120 2023.10

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Language：English Publishing type：Research paper (scientific journal)

The circadian clock is a biological timekeeping system that oscillates with a circa-24-h period, reset by environmental timing cues, especially light, to the 24-h day-night cycle. In mammals, a "central" clock in the hypothalamic suprachiasmatic nucleus (SCN) synchronizes "peripheral" clocks throughout the body to regulate behavior, metabolism, and physiology. A key feature of the clock's oscillation is resistance to abrupt perturbations, but the mechanisms underlying such robustness are not well understood. Here, we probe clock robustness to unexpected photic perturbation by measuring the speed of reentrainment of the murine locomotor rhythm after an abrupt advance of the light-dark cycle. Using an intersectional genetic approach, we implicate a critical role for arginine vasopressin pathways, both central within the SCN and peripheral from the anterior pituitary.

DOI： 10.1073/pnas.2308489120

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Nmu/Nms/Gpr176 Triple-Deficient Mice Show Enhanced Light-Resetting of Circadian Locomotor Activity.

Yoshiaki Yamaguchi, Iori Murai, Momoko Takeda, Shotaro Doi, Takehito Seta, Reiko Hanada, Kenji Kangawa, Hitoshi Okamura, Takahito Miyake, Masao Doi

Biological & pharmaceutical bulletin 45 ( 8 ) 1172 - 1179 2022

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The suprachiasmatic nucleus (SCN) is the master circadian clock in mammals and is properly entrained by environmental light cycle. However, the molecular mechanism(s) determining the magnitude of phase shift by light is still not fully understood. The orphan G-protein-coupled receptor Gpr176 is enriched in the SCN, controls the pace (period) of the circadian rhythm in behavior but is not apparently involved in the light entrainment; Gpr176-/- animals display a shortened circadian period in constant darkness but their phase-resetting responses to light are normal. Here, we performed microarray analysis and identified enhanced mRNA expression of neuromedin U (Nmu) and neuromedin S (Nms) in the SCN of Gpr176-/- mice. By generating C57BL/6J-backcrossed Nmu/Nms/Gpr176 triple knockout mice, we noted that the mutant mice had a greater magnitude of phase shift in response to early subjective night light than wildtype mice, while Nmu/Nms double knockout mice as well as Gpr176 knockout mice are normal in the phase shifts induced by light. At the molecular level, Nmu-/-Nms-/-Gpr176-/- mice had a reduced induction of Per1 and cFos mRNA expression in the SCN by light and mildly upregulated circadian expression of Per2, Prok2, Rgs16, and Rasl11b. These expressional changes may underlie the phenotype of the Nmu/Nms/Gpr176 knockout mice. Our data argue that there is a mechanism requiring Nmu, Nms, and Gpr176 for the proper modulation of light-induced phase shift in mice. Simultaneous modulation of Nmu/Nms/Gpr176 may provide a potential target option for modulating the circadian clock.

DOI： 10.1248/bpb.b22-00260

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Gpr19 is a circadian clock-controlled orphan GPCR with a role in modulating free-running period and light resetting capacity of the circadian clock. International journal

Yoshiaki Yamaguchi, Iori Murai, Kaoru Goto, Shotaro Doi, Huihua Zhou, Genzui Setsu, Hiroyuki Shimatani, Hitoshi Okamura, Takahito Miyake, Masao Doi

Scientific reports 11 ( 1 ) 22406 - 22406 2021.11

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Gpr19 encodes an evolutionarily conserved orphan G-protein-coupled receptor (GPCR) with currently no established physiological role in vivo. We characterized Gpr19 expression in the suprachiasmatic nucleus (SCN), the locus of the master circadian clock in the brain, and determined its role in the context of the circadian rhythm regulation. We found that Gpr19 is mainly expressed in the dorsal part of the SCN, with its expression fluctuating in a circadian fashion. A conserved cAMP-responsive element in the Gpr19 promoter was able to produce circadian transcription in the SCN. Gpr19-/- mice exhibited a prolonged circadian period and a delayed initiation of daily locomotor activity. Gpr19 deficiency caused the downregulation of several genes that normally peak during the night, including Bmal1 and Gpr176. In response to light exposure at night, Gpr19-/- mice had a reduced capacity for light-induced phase-delays, but not for phase-advances. This defect was accompanied by reduced response of c-Fos expression in the dorsal region of the SCN, while apparently normal in the ventral area of the SCN, in Gpr19-/- mice. Thus, our data demonstrate that Gpr19 is an SCN-enriched orphan GPCR with a distinct role in circadian regulation and may provide a potential target option for modulating the circadian clock.

DOI： 10.1038/s41598-021-01764-8

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Vasopressin Signal Inhibition in Aged Mice Decreases Mortality under Chronic Jet Lag Reviewed

Yoshiaki Yamaguchi

iScience 5 118 - 122 2018.7

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/j.isci.2018.06.008

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Mice Genetically Deficient in Vasopressin V1a and V1b Receptors Are Resistant to Jet Lag Reviewed International journal

Yoshiaki Yamaguchi, Toru Suzuki, Yasutaka Mizoro, Hiroshi Kori, Kazuki Okada, Yulin Chen, Jean-Michel Fustin, Fumiyoshi Yamazaki, Naoki Mizuguchi, Jing Zhang, Xin Dong, Gozoh Tsujimoto, Yasushi Okuno, Masao Doi, Hitoshi Okamura

Science 342 ( 6154 ) 85 - 90 2013.10

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1126/science.1238599

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Selective and Quickly Reversible Inactivation of Mammalian Neurons In Vivo Using the Drosophila Allatostatin Receptor Reviewed

Tan, E.M., Yamaguchi, Y., Horwitz, G.D., Gosgnach, S., Lein, E.S., Goulding, M., Albright, T.D., Callaway, E.M.

Neuron 51 ( 2 ) 157 - 170 2006.7

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DOI： 10.1016/j.neuron.2006.06.018

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Gα12 and Gα13 interact with Ser/Thr protein phosphatase type 5 and stimulate its phosphatase activity Reviewed

Yamaguchi, Y., Katoh, H., Mori, K., Negishi, M.

Current Biology 12 ( 15 ) 1353 - 1358 2002.8

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Authorship：Lead author Publishing type：Research paper (scientific journal)

DOI： 10.1016/S0960-9822(02)01034-5

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Heterogeneity between VIP and GRP neurons underlies AVP receptor signaling in the mouse suprachiasmatic nucleus

Huihua Zhou, Daichi Moriyasu, Sui-Wen Hsiao, Yoshiaki Yamaguchi, Morio Azuma, Taka-aki Koshimizu, Keiichi Itoi, Kenji Sakimura, William J. Schwartz, Hitoshi Okamura, Emi Hasegawa, Masao Doi

Communications Biology 2026.2

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DOI： 10.1038/s42003-026-09694-9

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Arginine vasopressin: Critical regulator of circadian homeostasis. International journal

Yoshiaki Yamaguchi

Peptides 177 171229 - 171229 2024.7

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Circadian rhythms optimally regulate numerous physiological processes in an organism and synchronize them with the external environment. The suprachiasmatic nucleus (SCN), the center of the circadian clock in mammals, is composed of multiple cell types that form a network that provides the basis for the remarkable stability of the circadian clock. Among the neuropeptides expressed in the SCN, arginine vasopressin (AVP) has attracted much attention because of its deep involvement in the function of circadian rhythms, as elucidated in particular by studies using genetically engineered mice. This review briefly summarizes the current knowledge on the peptidergic distribution and topographic neuronal organization in the SCN, the molecular mechanisms of the clock genes, and the relationship between the SCN and peripheral clocks. With respect to the physiological roles of AVP and AVP-expressing neurons, in addition to a sex-dependent action of AVP in the SCN, studies using AVP receptor knockout mice and mice genetically manipulated to alter the clock properties of AVP neurons are summarized here, highlighting its importance in maintaining circadian homeostasis and its potential as a target for therapeutic interventions.

DOI： 10.1016/j.peptides.2024.171229

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【体内時計のprecision medicine】時差ぼけはなぜ起こるのか生物が初めて直面したリズム異常

山口賀章, 冨永恵子, 岡村均

Precision Medicine 6 ( 5 ) 358 - 361 2023.5

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Language：Japanese Publisher：(株)北隆館

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Minimal upstream open reading frame of Per2 mediates phase fitness of the circadian clock to day/night physiological body temperature rhythm. International journal

Takahito Miyake, Yuichi Inoue, Xinyan Shao, Takehito Seta, Yuto Aoki, Khanh Tien Nguyen Pham, Yuichi Shichino, Junko Sasaki, Takehiko Sasaki, Masahito Ikawa, Yoshiaki Yamaguchi, Hitoshi Okamura, Shintaro Iwasaki, Masao Doi

Cell reports 42 ( 3 ) 112157 - 112157 2023.2

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Body temperature in homeothermic animals does not remain constant but displays a regular circadian fluctuation within a physiological range (e.g., 35°C-38.5°C in mice), constituting a fundamental systemic signal to harmonize circadian clock-regulated physiology. Here, we find the minimal upstream open reading frame (uORF) encoded by the 5' UTR of the mammalian core clock gene Per2 and reveal its role as a regulatory module for temperature-dependent circadian clock entrainment. A temperature shift within the physiological range does not affect transcription but instead increases translation of Per2 through its minimal uORF. Genetic ablation of the Per2 minimal uORF and inhibition of phosphoinositide-3-kinase, lying upstream of temperature-dependent Per2 protein synthesis, perturb the entrainment of cells to simulated body temperature cycles. At the organismal level, Per2 minimal uORF mutant skin shows delayed wound healing, indicating that uORF-mediated Per2 modulation is crucial for optimal tissue homeostasis. Combined with transcriptional regulation, Per2 minimal uORF-mediated translation may enhance the fitness of circadian physiology.

DOI： 10.1016/j.celrep.2023.112157

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Optimising the method for visualising mouse meibomian gland using eyelid whole-mount lipid staining. Reviewed International journal

Yuki Hamada, Lena Sasaki, Hikari Uehara, Tomo Suzuki, Shigeru Kinoshita, Kento Otsuka, Akio Kihara, Yoshiaki Yamaguchi, Takahito Miyake, Masao Doi

The ocular surface 26 268 - 270 2022.10

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DOI： 10.1016/j.jtos.2022.10.002

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A light-induced small G-protein gem limits the circadian clock phase-shift magnitude by inhibiting voltage-dependent calcium channels. International journal

Masahiro Matsuo, Kazuyuki Seo, Akiyuki Taruno, Yasutaka Mizoro, Yoshiaki Yamaguchi, Masao Doi, Rhyuta Nakao, Hiroshi Kori, Takaya Abe, Harunori Ohmori, Keiko Tominaga, Hitoshi Okamura

Cell reports 39 ( 8 ) 110844 - 110844 2022.5

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Calcium signaling is pivotal to the circadian clockwork in the suprachiasmatic nucleus (SCN), particularly in rhythm entrainment to environmental light-dark cycles. Here, we show that a small G-protein Gem, an endogenous inhibitor of high-voltage-activated voltage-dependent calcium channels (VDCCs), is rapidly induced by light in SCN neurons via the calcium (Ca2+)-mediated CREB/CRE transcriptional pathway. Gem attenuates light-induced calcium signaling through its interaction with VDCCs. The phase-shift magnitude of locomotor activity rhythms by light, at night, increases in Gem-deficient (Gem-/-) mice. Similarly, in SCN slices from Gem-/- mice, depolarizing stimuli induce larger phase shifts of clock gene transcription rhythms that are normalized by the application of an L-type VDCC blocker, nifedipine. Voltage-clamp recordings from SCN neurons reveal that Ca2+ currents through L-type channels increase in Gem-/- mice. Our findings suggest that transcriptionally activated Gem feeds back to suppress excessive light-evoked L-type VDCC activation, adjusting the light-induced phase-shift magnitude to an appropriate level in mammals.

DOI： 10.1016/j.celrep.2022.110844

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Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction

Lena Sasaki, Yuki Hamada, Daisuke Yarimizu, Tomo Suzuki, Hiroki Nakamura, Aya Shimada, Khanh Tien Nguyen Pham, Xinyan Shao, Koki Yamamura, Tsutomu Inatomi, Hironobu Morinaga, Emi K. Nishimura, Fujimi Kudo, Ichiro Manabe, Shogo Haraguchi, Yuki Sugiura, Makoto Suematsu, Shigeru Kinoshita, Mamiko Machida, Takeshi Nakajima, Hiroshi Kiyonari, Hitoshi Okamura, Yoshiaki Yamaguchi, Takahito Miyake, Masao Doi

Nature Aging 2 ( 2 ) 105 - 114 2022.2

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Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3β-hydroxyl-steroid dehydrogenase (3β-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3β-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3β-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3β-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction.

DOI： 10.1038/s43587-021-00167-8

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Other Link： https://www.nature.com/articles/s43587-021-00167-8
Thermographic imaging of mouse across circadian time reveals body surface temperature elevation associated with non-locomotor body movements Reviewed

Hiroyuki Shimatani, Yuichi Inoue, Yota Maekawa, Takahito Miyake, Yoshiaki Yamaguchi, Masao Doi

PLOS ONE 16 ( 5 ) e0252447 - e0252447 2021.5

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Circadian clocks orchestrate multiple different physiological rhythms in a well-synchronized manner. However, how these separate rhythms are interconnected is not exactly understood. Here, we developed a method that allows for the real-time simultaneous measurement of locomotor activity and body temperature of mice using infrared video camera imaging. As expected from the literature, temporal profiles of body temperature and locomotor activity were positively correlated with each other. Basically, body temperatures were high when animals were in locomotion. However, interestingly, increases in body temperature were not always associated with the appearance of locomotor activity. Video imaging revealed that mice exhibit non-locomotor activities such as grooming and postural adjustments, which alone induce considerable elevation of body temperature. Noticeably, non-locomotor movements always preceded the initiation of locomotor activity. Nevertheless, non-locomotor movements were not always accompanied by locomotor movements, suggesting that non-locomotor movements provide a mechanism of thermoregulation independent of locomotor activity. In addition, in the current study, we also report the development of a machine learning-based recording method for the detection of circadian feeding and drinking behaviors of mice. Our data illustrate the potential utility of thermal video imaging in the investigation of different physiological rhythms.

DOI： 10.1371/journal.pone.0252447

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Identification and functional characterisation of N-linked glycosylation of the orphan G protein-coupled receptor Gpr176 Reviewed

Tianyu Wang, Shumpei Nakagawa, Takahito Miyake, Genzui Setsu, Sumihiro Kunisue, Kaoru Goto, Akira Hirasawa, Hitoshi Okamura, Yoshiaki Yamaguchi, Masao Doi

Scientific Reports 10 ( 1 ) 4429 2020.12

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Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media {LLC}

<jats:title>Abstract</jats:title><jats:p>G-protein-coupled receptors (GPCRs) are important drug targets with diverse therapeutic applications. However, there are still more than a hundred orphan GPCRs, whose protein functions and biochemical features remain unidentified. <jats:italic>Gpr176</jats:italic> encodes a class-A orphan GPCR that has a role in circadian clock regulation in mouse hypothalamus and is also implicated in human breast cancer transcriptional response. Here we show that Gpr176 is <jats:italic>N</jats:italic>-glycosylated. Peptide-<jats:italic>N</jats:italic>-glycosidase treatment of mouse hypothalamus extracts revealed that endogenous Gpr176 undergoes <jats:italic>N</jats:italic>-glycosylation. Using a heterologous expression system, we show that <jats:italic>N</jats:italic>-glycosylation occurs at four conserved asparagine residues in the N-terminal region of Gpr176. Deficient <jats:italic>N</jats:italic>-glycosylation due to mutation of these residues reduced the protein expression of Gpr176. At the molecular function level, Gpr176 has constitutive, agonist-independent activity that leads to reduced cAMP synthesis. Although deficient <jats:italic>N</jats:italic>-glycosylation did not compromise this intrinsic activity, the resultant reduction in protein expression was accompanied by attenuation of cAMP-repressive activity in the cells. We also demonstrate that human GPR176 is <jats:italic>N</jats:italic>-glycosylated. Importantly, missense variations in the conserved <jats:italic>N</jats:italic>-glycosylation sites of human GPR176 (rs1473415441; rs761894953) affected <jats:italic>N</jats:italic>-glycosylation and thereby attenuated protein expression and cAMP-repressive activity in the cells. We show that <jats:italic>N</jats:italic>-glycosylation is a prerequisite for the efficient protein expression of functional Gpr176/GPR176.</jats:p>

DOI： 10.1038/s41598-020-61370-y

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Non-coding cis-element of Period2 is essential for maintaining organismal circadian behaviour and body temperature rhythmicity Reviewed International journal

Masao Doi, Hiroyuki Shimatani, Yuta Atobe, Iori Murai, Hida Hayashi, Yukari Takahashi, Jean-Michel Fustin, Yoshiaki Yamaguchi, Hiroshi Kiyonari, Nobuya Koike, Kazuhiro Yagita, Choogon Lee, Manabu Abe, Kenji Sakimura, Hitoshi Okamura

Nature Communications 10 ( 1 ) 2563 - 2563 2019.12

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Non-coding cis-regulatory elements are essential determinants of development, but their exact impacts on behavior and physiology in adults remain elusive. Cis-element-based transcriptional regulation is believed to be crucial for generating circadian rhythms in behavior and physiology. However, genetic evidence supporting this model is based on mutations in the protein-coding sequences of clock genes. Here, we report generation of mutant mice carrying a mutation only at the E'-box cis-element in the promoter region of the core clock gene Per2. The Per2 E'-box mutation abolishes sustainable molecular clock oscillations and renders circadian locomotor activity and body temperature rhythms unstable. Without the E'-box, Per2 messenger RNA and protein expression remain at mid-to-high levels. Our work delineates the Per2 E'-box as a critical nodal element for keeping sustainable cell-autonomous circadian oscillation and reveals the extent of the impact of the non-coding cis-element in daily maintenance of animal locomotor activity and body temperature rhythmicity.

DOI： 10.1038/s41467-019-10532-2

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Other Link： http://www.nature.com/articles/s41467-019-10532-2
生物系薬学家族性睡眠相後退障害におけるヒト概日時計遺伝子CRY1の変異同定 Reviewed

山口, 賀章

ファルマシア 54 ( 3 ) 255 - 255 2018

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Language：Japanese

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Arginine vasopressin signaling in the suprachiasmatic nucleus on the resilience of circadian clock to jet lag Reviewed

Yoshiaki Yamaguchi

Neuroscience Research 129 57 - 61 2018

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Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1016/J.NEURES.2017.10.007

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Circadian rhythms of micturition during jet lag Reviewed

Ito, K., Yasuda, M., Maeda, Y., Fustin, J.-M., Yamaguchi, Y., Kono, Y., Negoro, H., Kanematsu, A., Ogawa, O., Doi, M., Okamura, H.

Biomedical Research Japan 39 ( 2 ) 57 - 63 2018

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DOI： 10.2220/biomedres.39.57

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Effect of daily light on c-Fos expression in the suprachiasmatic nucleus under jet lag conditions Reviewed

Chen, Y., Yamaguchi, Y., Suzuki, T., Doi, M., Okamura, H.

Acta Histochemica Et Cytochemica 51 ( 2 ) 73 - 80 2018

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Authorship：Corresponding author Publishing type：Research paper (scientific journal)

DOI： 10.1267/ahc.18001

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Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway Reviewed International journal

Hsu-Wen Chao, Masao Doi, Jean-Michel Fustin, Huatao Chen, Kimihiko Murase, Yuki Maeda, Hida Hayashi, Rina Tanaka, Maho Sugawa, Naoki Mizukuchi, Yoshiaki Yamaguchi, Jun-ichirou Yasunaga, Masao Matsuoka, Mashito Sakai, Michihiro Matsumoto, Shinshichi Hamada, Hitoshi Okamura

Nature Communications 8 ( 1 ) 2238 - 2238 2017.12

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DOI： 10.1038/s41467-017-02207-7

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Other Link： http://www.nature.com/articles/s41467-017-02207-7
Accelerating recovery from jet lag: prediction from a multi-oscillator model and its experimental confirmation in model animals Reviewed

Hiroshi Kori, Yoshiaki Yamaguchi, Hitoshi Okamura

Scientific Reports 7 ( 1 ) 2017.5

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Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

DOI： 10.1038/srep46702

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Other Link： http://www.nature.com/articles/srep46702
Carbachol Induces Phase-dependent Phase Shifts of Per1 Transcription Rhythms in Cultured Suprachiasmatic Nucleus Slices Reviewed

Dojo, K., Yamaguchi, Y., Fustin, J.-M., Doi, M., Kobayashi, M., Okamura, H.

Journal of Biological Rhythms 32 ( 2 ) 101 - 108 2017.4

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DOI： 10.1177/0748730417691205

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Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/0748730417691205
Real-Time Recording of Circadian Per1 and Per2 Expression in the Suprachiasmatic Nucleus of Freely Moving Rats Reviewed

Yamaguchi, Y., Okada, K., Mizuno, T., Ota, T., Yamada, H., nd Doi, M.A.S.A.O., Kobayashi, M., Tei, H., Shigeyoshi, Y., Okamura, H.

Journal of Biological Rhythms 31 ( 1 ) 108 - 111 2016.2

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Erratum: Ecto-domain phosphorylation promotes functional recovery from spinal cord injury(Scientific Reports 4(4972) 10.1038/srep04972) Reviewed

Kenji Suehiro, Yuka Nakamura, Shuai Xu, Youichi Uda, Takafumi Matsumura, Yoshiaki Yamaguchi, Hitoshi Okamura, Toshihide Yamashita, Yoshinori Takei

Scientific Reports 5 11780 2015.7

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DOI： 10.1038/srep11780

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内分泌基礎分野での進歩脳内バソプレッシンと時差 Reviewed

岡村, 均, 山口, 賀章

Annual Review糖尿病・代謝・内分泌 2015 143 - 151 2015

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時差消失マウスの開発による概日リズムの頑強性を担う分子神経機構の解明 Reviewed

山口, 賀章

薬学雑誌 135 ( 11 ) 1265 - 1272 2015

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DOI： 10.1248/yakushi.15-00206

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Ecto-domain phosphorylation promotes functional recovery from spinal cord injury Reviewed International journal

Kenji Suehiro, Yuka Nakamura, Shuai Xu, Youichi Uda, Takafumi Matsumura, Yoshiaki Yamaguchi, Hitoshi Okamura, Toshihide Yamashita, Yoshinori Takei

Scientific Reports 4 ( 1 ) 4972 - 4972 2014.12

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神経内科学脳内バゾプレシンは時差ボケの原因か Reviewed

山口, 賀章, 岡村, 均

医学のあゆみ 250 ( 13 ) 1195 - 1196 2014

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[Vasopressin-mediated neuronal circuit in the suprachiasmatic nucleus and jet lag] Reviewed

Yamaguchi, Y., Okamura, H.

Seikagaku. Journal of Japanese Biochemical Society 86 ( 5 ) 687 - 692 2014

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【脳内環境-維持機構と破綻がもたらす疾患研究】 (第1章)神経細胞内病態と脳内環境時差の分子機構とその治療 Reviewed

岡村, 均, 山口, 賀章

遺伝子医学MOOK ( 26 ) 54 - 60 2014

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時差をつかさどる視交叉上核のバソプレッシン神経回路 Reviewed

山口, 賀章, 岡村, 均

生化学 86 ( 5 ) 687 - 692 2014

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RNA-Methylation-Dependent RNA Processing Controls the Speed of the Circadian Clock Reviewed

Jean-Michel Fustin, Masao Doi, Yoshiaki Yamaguchi, Hayashi Hida, Shinichi Nishimura, Minoru Yoshida, Takayuki Isagawa, Masaki Suimye Morioka, Hideaki Kakeya, Ichiro Manabe, Hitoshi Okamura

Cell 155 ( 4 ) 793 - 806 2013.11

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DOI： 10.1016/j.cell.2013.10.026

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【最新臨床睡眠学-睡眠障害の基礎と臨床-】特論神経インパルスからホルモンへの時間変換機構 Reviewed

山口, 賀章, 岡村, 均

日本臨床 71 ( 増刊5 最新臨床睡眠学 ) 705 - 710 2013

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【代謝内分泌神経ネットワーク】生物時計と臓器ネットワーク時差の体内機構 Reviewed

山口, 賀章, 岡村, 均

BIO Clinica 28 ( 14 ) 1319 - 1324 2013

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【睡眠と生活習慣病-基礎・臨床研究の最新知見-】時計遺伝子・概日リズム概日リズム発振の遺伝子機構 Reviewed

山口, 賀章, 岡村, 均

日本臨床 70 ( 7 ) 1115 - 1120 2012

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[Molecular oscillatory machinery of circadian rhythms]. Reviewed

Yamaguchi, Y., Okamura, H.

Nihon Rinsho Japanese Journal of Clinical Medicine 70 ( 7 ) 1115 - 20 2012

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【ナノバイオ技術と最新創薬応用研究】 (第1章)ナノバイオ創薬に向けたターゲットの探索と構造解析概日リズムの分子機構と創薬 Reviewed

山口, 賀章, 岡村, 均

遺伝子医学MOOK ( 20 ) 47 - 51 2012

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Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus Reviewed

Masao Doi, Atsushi Ishida, Akiko Miyake, Miho Sato, Rie Komatsu, Fumiyoshi Yamazaki, Ikuo Kimura, Soken Tsuchiya, Hiroshi Kori, Kazuyuki Seo, Yoshiaki Yamaguchi, Masahiro Matsuo, Jean-Michel Fustin, Rina Tanaka, Yasuko Santo, Hiroyuki Yamada, Yukari Takahashi, Michihiro Araki, Kazuki Nakao, Shinichi Aizawa, Masaki Kobayashi, Karl Obrietan, Gozoh Tsujimoto, Hitoshi Okamura

Nature Communications 2 ( 1 ) 2011.9

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DOI： 10.1038/ncomms1316

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Accurate Determination of S-Phase Fraction in Proliferative Cells by Dual Fluorescence and Peroxidase Immunohistochemistry with 5-Bromo-2′-Deoxyuridine (BrdU) and Ki67 Antibodies Reviewed

Rina Tanaka, Motomi Tainaka, Takumi Ota, Naoki Mizuguchi, Hiroyuki Kato, Shoichi Urabe, Yulin Chen, Jean-Michel Fustin, Yoshiaki Yamaguchi, Masao Doi, Shinshichi Hamada, Hitoshi Okamura

Journal of Histochemistry & Cytochemistry 59 ( 8 ) 791 - 798 2011.8

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DOI： 10.1369/0022155411411090

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Transportin 1 in the mouse brain: Appearance in regions of neurogenesis, cerebrospinal fluid production/sensing, and circadian clock Reviewed

Sato, M., Mizoro, Y., Atobe, Y., Fujimoto, Y., Yamaguchi, Y., Fustin, J.-M., Doi, M., Okamura, H.

Journal of Comparative Neurology 519 ( 9 ) 1770 - 1780 2011.6

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DOI： 10.1002/cne.22600

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Hypertension due to loss of clock: Novel insight from the molecular analysis of Cry1/Cry2-deleted mice Reviewed

Okamura, H., Doi, M., Yamaguchi, Y., Fustin, J.-M.

Current Hypertension Reports 13 ( 2 ) 103 - 108 2011.4

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DOI： 10.1007/s11906-011-0181-3

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Mammalian circadian clock system: Molecular mechanisms for pharmaceutical and medical sciences Reviewed

Okamura, H., Doi, M., Fustin, J.-M., Yamaguchi, Y., Matsuo, M.

Advanced Drug Delivery Reviews 62 ( 9-10 ) 876 - 884 2010.7

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Activation of AMPA receptors in the suprachiasmatic nucleus phase-shifts the mouse circadian clock in vivo and in vitro Reviewed

Mizoro, Y., Yamaguchi, Y., Kitazawa, R., Yamada, H., Matsuo, M., Fustin, J.-M., Doi, M., Okamura, H.

Plos One 5 ( 6 ) e10951 - e10951 2010.6

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【季節変動と日内変動】体内時計とは? 体内時計について教えてください Reviewed

山口, 賀章, 岡村, 均

Q&Aでわかる肥満と糖尿病 9 ( 2 ) 197 - 199 2010

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Molecular clocks in mouse skin Reviewed

Tanioka, M., Yamada, H., Doi, M., Bando, H., Yamaguchi, Y., Nishigori, C., Okamura, H.

Journal of Investigative Dermatology 129 ( 5 ) 1225 - 1231 2009.5

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DOI： 10.1038/jid.2008.345

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Circadian expression of the Na+/H+ exchanger NHE3 in the mouse renal medulla Reviewed

Hiromi Nishinaga, Rie Komatsu, Masao Doi, Jean-Michel Fustin, Hiroyuki Yamada, Ryusuke Okura, Yoshiaki Yamaguchi, Masahiro Matsuo, Noriaki Emoto, Hitoshi Okamura

Biomedical Research 30 ( 2 ) 87 - 93 2009

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DOI： 10.2220/biomedres.30.87

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テクノ・トレンド生きた動物で使える迅速で可逆的なAlstR/AL神経細胞不活性化法の開発 Reviewed

山口, 賀章

バイオテクノロジージャーナル 7 ( 1 ) 70 - 73 2007

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Two G12 family G proteins, Gα12 and Gα13, show different subcellular localization Reviewed

Yamazaki, J., Katoh, H., Yamaguchi, Y., Negishi, M.

Biochemical and Biophysical Research Communications 332 ( 3 ) 782 - 786 2005.7

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DOI： 10.1016/j.bbrc.2005.05.023

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N-terminal short sequences of α subunits of the G12 family determine selective coupling to receptors Reviewed

Yamaguchi, Y., Katoh, H., Negishi, M.

Journal of Biological Chemistry 278 ( 17 ) 14936 - 14939 2003.4

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DOI： 10.1074/jbc.M301409200

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RhoA Inhibits the Nerve Growth Factor-induced Rac1 Activation through Rho-associated Kinase-dependent Pathway Reviewed

Yamaguchi, Y., Katoh, H., Yasui, H., Mori, K., Negishi, M.

Journal of Biological Chemistry 276 ( 22 ) 18977 - 18983 2001.6

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DOI： 10.1074/jbc.M100254200

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Differential Responses to Nerve Growth Factor and Epidermal Growth Factor in Neurite Outgrowth of PC12 Cells Are Determined by Rac1 Activation Systems Reviewed

Hidekazu Yasui, Hironori Katoh, Yoshiaki Yamaguchi, Junko Aoki, Hirotada Fujita, Kazutoshi Mori, Manabu Negishi

Journal of Biological Chemistry 276 ( 18 ) 15298 - 15305 2001.1

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DOI： 10.1074/jbc.m008546200

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Small GTPase RhoG Is a Key Regulator for Neurite Outgrowth in PC12 Cells Reviewed

Hironori Katoh, Hidekazu Yasui, Yoshiaki Yamaguchi, Junko Aoki, Hirotada Fujita, Kazutoshi Mori, Manabu Negishi

Molecular and Cellular Biology 20 ( 19 ) 7378 - 7387 2000.10

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DOI： 10.1128/mcb.20.19.7378-7387.2000

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Gα12 and Gα13 inhibit Ca2+-dependent exocytosis through Rho/Rho- associated kinase-dependent pathway Reviewed

Yamaguchi, Y., Katoh, H., Yasui, H., Aoki, J., Nakamura, K., Negishi, M.

Journal of Neurochemistry 75 ( 2 ) 708 - 717 2000.8

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DOI： 10.1046/j.1471-4159.2000.0750708.x

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Different membrane targeting of prostaglandin EP3 receptor isoforms dependent on their carboxy-terminal tail structures Reviewed

Hasegawa, H., Katoh, H., Yamaguchi, Y., Nakamura, K., Futakawa, S., Negishi, M.

FEBS Letters 473 ( 1 ) 76 - 80 2000.5

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DOI： 10.1016/S0014-5793(00)01508-8

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Molecular decipherment of Rho effector pathways regulating tight-junction permeability Reviewed

Fujita, H., Katoh, H., Hasegawa, H., Yasui, H., Aoki, J., Yamaguchi, Y., Negishi, M.

Biochem J 346 Pt 3 617 - 622 2000

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DOI： 10.1042/0264-6021:3460617

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Signal transduction pathway regulating prostaglandin EP3 receptor-induced neurite retraction: requirement for two different tyrosine kinases Reviewed

Aoki, J., Katoh, H., Yasui, H., Yamaguchi, Y., Nakamura, K., Hasegawa, H., Ichikawa, A., Negishi, M.

Biochem J 340 ( Pt 2) 365 - 369 1999

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DOI： 10.1042/0264-6021:3400365

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Constitutively active Gα12, Gα13, and Gα(q) induce rho-dependent neurite retraction through different signaling pathways Reviewed

Katoh, H., Aoki, J., Yamaguchi, Y., Kitano, Y., Ichikawa, A., Negishi, M.

Journal of Biological Chemistry 273 ( 44 ) 28700 - 28707 1998.11

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DOI： 10.1074/jbc.273.44.28700

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バイオテクノロジージャーナル生きた動物で使える迅速で可逆的なAlstR/AL神経細胞不活性化法の開発

山口賀章

羊土社 2007.1

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MISC

時差ぼけがストレス神経系を動かすとき

岡村均, 山口賀章, 冨永恵子

科学 94 ( 3 ) 2024

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【時間生物学の現在】時間生物学の基礎

山口賀章

臨床化学 50 ( 4 ) 321 - 328 2021.10

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【老化、加齢疾患研究を俯瞰し、健康長寿社会実現の夢を開く】Seminar 老化と体内時計:加齢による脳内中枢時計の機能低下を中心に

濱田悠貴, 山口賀章, 土居雅夫

Geriatric Medicine 59 ( 7 ) 683 - 687 2021.7

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バソプレッシンシグナルによる時差環境下での概日行動リズム制御

山口賀章

糖尿病・内分泌代謝科 51 ( 1 ) 60 - 65 2020.7

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生理学バソプレシンシグナルの抑制は時差による老齢マウスの生存率を改善する

山口賀章, 岡村均

医学のあゆみ 269 ( 12 ) 942 - 944 2019.6

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バソプレッシンシグナルの抑制は、慢性時差環境下での老齢マウスの死亡率を減少させる

山口賀章, 岡村均

日本内分泌学会雑誌 94 ( 4 ) 1324 - 1324 2018.12

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バソプレッシンシグナルの抑制は、慢性時差環境下での老齢マウスの死亡率を減少させる

山口賀章, 岡村均

日本内分泌学会雑誌 94 ( 4 ) 1324 - 1324 2018.12

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慢性時差環境下における老齢Va1V1bノックアウトマウスの生存率

山口賀章, 岡村均

日本生化学会大会プログラム・講演要旨集 91回 [1P - 311] 2018.9

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【実臨床へ向けた時間医薬研究の新動向】時差環境下における概日リズム障害の分子メカニズムと治療標的

山口賀章

医薬ジャーナル 54 ( 6 ) 1433 - 1438 2018.6

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概日リズム中枢・視交叉上核の時差再同調過程における数理モデル解析

前川洋太, 山口賀章, 岡村均, 郡宏

生命科学系学会合同年次大会 2017年度 [2P - 1181] 2017.12

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数理モデルによる視交叉上核バソプレッシン細胞の時差再同調解析とその応用

山口賀章, 岡村均, 郡宏

日本内分泌学会雑誌 93 ( 4 ) 1226 - 1226 2017.12

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Circadian Regulation of Behavior, Physiology and Metabolism 時差を担う視交叉上核バソプレッシンV1a、V1b受容体

山口賀章, 岡村均

日本抗加齢医学会総会プログラム・抄録集 16回 101 - 101 2016.6

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バソプレッシン受容体欠損マウスにおける時差環境下の摂食・飲水リズムは瞬時に再同調する

水野貴暢, 鈴木暢, 山口賀章, 岡村均

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回 [1P1303] - [1P1303] 2015.12

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視交叉上核バソプレッシン受容体の細胞概日振動における役割

山口賀章, 溝曽路祥孝, 郡宏, 岡村均

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集 88回・38回 [1T18 - 14(1P1299)] 2015.12

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バソプレッシンV1a/V1b受容体による概日リズム形成

山口賀章, 岡村均

日本内分泌学会雑誌 91 ( 2 ) 516 - 516 2015.9

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J-GLOBAL

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内分泌 A.基礎分野での進歩 1.脳内バソプレッシンと時差

OKAMURA HITOSHI, YAMAGUCHI YOSHIAKI

Annual Review 糖尿病・代謝・内分泌 2015 143 - 151 2015.1

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J-GLOBAL

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脳内バソプレッシンと時差 (内分泌) -- (基礎分野での進歩)

岡村均, 山口賀章

Annual review. 糖尿病・代謝・内分泌 143 - 151 2015

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Molecular and neural mechanisms for the robustness of the circadian clock

Yamaguchi, Y.

Yakugaku Zasshi 135 ( 11 ) 1265 - 1272 2015

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DOI： 10.1248/yakushi.15-00206

Web of Science

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神経細胞内病態と脳内環境 6.時差の分子機構とその治療

OKAMURA HITOSHI, YAMAGUCHI YOSHIAKI

遺伝子医学MOOK ( 26 ) 54-60,6-7 2014.11

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J-GLOBAL

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【脳内環境-維持機構と破綻がもたらす疾患研究】 (第1章)神経細胞内病態と脳内環境時差の分子機構とその治療

岡村均, 山口賀章

遺伝子医学MOOK ( 26 ) 54 - 60 2014.11

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時差をつかさどる視交叉上核のバソプレッシン神経回路

YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

生化学 86 ( 5 ) 687 - 692 2014.10

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行動・睡眠リズムを支配する体内時計の分子機構とその創薬標的としての可能性視交叉上核におけるバソプレッシンとその受容体であるV1a/V1bのシグナルによる細胞内情報伝達は時差ボケに重要な役割を果たす(Intercellular communication by vasopressin-V1a/V1b signaling in the suprachiasmatic nucleus has a key role in jet lag)

山口賀章, 岡村均

日本生化学会大会プログラム・講演要旨集 87回 [4S08a - 6] 2014.10

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概日リズム形成におけるバゾプレシンV1a,V1b受容体の役割

YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

日本内分泌学会雑誌 90 ( 2 ) 585 2014.9

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J-GLOBAL

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体内時計と神経内分泌概日リズム形成におけるバゾプレシンV1a、V1b受容体の役割

山口賀章, 岡村均

日本内分泌学会雑誌 90 ( 2 ) 585 - 585 2014.9

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神経内科学脳内バゾプレシンは時差ボケの原因か

山口賀章, 岡村均

医学のあゆみ 250 ( 13 ) 1195 - 1196 2014.9

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代謝内分泌神経ネットワーク 4 生物時計と臓器ネットワーク:時差の体内機構

YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

Bio Clin 28 ( 14 ) 1319 - 1324 2013.12

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【代謝内分泌神経ネットワーク】生物時計と臓器ネットワーク時差の体内機構

山口賀章, 岡村均

BIO Clinica 28 ( 14 ) 1319 - 1324 2013.12

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時差消失マウスの分子機構の解明

YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

時間生物学 19 ( 2 ) 135 2013.10

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視交叉上核の外的撹乱因子に対する抵抗性と時差

YAMAGUCHI YOSHIAKI, MISOJI YOSHITAKA, KOORI HIROSHI, SUZUKI TOORU, OKAMURA HITOSHI

時間生物学 19 ( 2 ) 171 2013.10

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時差消失マウスの開発

SUZUKI TOORU, YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

時間生物学 19 ( 2 ) 161 2013.10

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神経インパルスからホルモンへの時間変換機構

YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

日本臨床 71 705 - 710 2013.10

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【最新臨床睡眠学-睡眠障害の基礎と臨床-】特論神経インパルスからホルモンへの時間変換機構

山口賀章, 岡村均

日本臨床 71 ( 増刊5 最新臨床睡眠学 ) 705 - 710 2013.10

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睡眠と生活習慣病 II.時計遺伝子・概日リズム概日リズム発振の遺伝子機構

YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

日本臨床 70 ( 7 ) 1115 - 1120 2012.7

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【睡眠と生活習慣病-基礎・臨床研究の最新知見-】時計遺伝子・概日リズム概日リズム発振の遺伝子機構

山口賀章, 岡村均

日本臨床 70 ( 7 ) 1115 - 1120 2012.7

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Other Link： http://search.jamas.or.jp/link/ui/2012270757
ナノバイオ技術と最新創薬応用研究第1章ナノバイオ創薬に向けたターゲットの探索と構造解析 4.概日リズムの分子機構と創薬

YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

遺伝子医学MOOK ( 20 ) 47 - 51 2012.1

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精神神経疾患と生体リズム精神神経疾患モデルマウスと体内時計

岡村均, 山口賀章, 田井中元美

日本臨床精神神経薬理学会・日本神経精神薬理学会合同年会プログラム・抄録集 21回・41回 87 - 87 2011.10

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時差消失マウス(NJLマウス)による概日リズム異常の新規治療薬の開発

YAMAGUCHI YOSHIAKI

かなえ医薬振興財団研究業績集(Web) 40th 31 (WEB ONLY) 2011

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視交叉上核のAMPA受容体活性化は,マウス概日時計の位相変化を引き起こす

MIZOSORO YOSHITAKA, YAMAGUCHI YOSHIAKI, OKAMURA HITOSHI

時間生物学 16 ( 2 ) 89 2010.10

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AMPA receptor activation in the suprachiasmatic nucleus induces phase-dependent phase-shifts of the circadian rhythms

Yoshiaki Yamaguchi

Neuroscience Research 49 ( 2-3 ) 568 - 568 2010.8

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DOI： 10.1016/J.NEURES.2010.07.2344

Web of Science

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【季節変動と日内変動】体内時計とは? 体内時計について教えてください

山口賀章, 岡村均

Q&Aでわかる肥満と糖尿病 9 ( 2 ) 197 - 199 2010.3

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テクノ・トレンド生きた動物で使える迅速で可逆的なAlstR/AL神経細胞不活性化法の開発

山口賀章

バイオテクノロジージャーナル 7 ( 1 ) 70 - 73 2007.1

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A novel genetic method for reversibly inactivating mammalian neurons in vivo

Yoshiaki Yamaguchi

Neuroscience Research 55 S105 - S105 2006

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Web of Science

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G12ファミリーの新規エフェクター,セリン・スレオニンフォスファターゼ5の同定とその活性制御機構の解析

YAMAGUCHI NORIAKI, KATO HIRONORI, NEGISHI MANABU

生化学 74 ( 8 ) 1048 - 1048 2002.8

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セリン・スレオニンフォスファターゼ5はG12ファミリーの新規エフェクターである

YAMAGUCHI YOSHIAKI, KATO HIRONORI, NEGISHI MANABU

日本神経科学大会プログラム・抄録集 25th 136 2002.7

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神経突起形成時のNGFによるRac1とRhoAの活性制御とそのクロストーク

YAMAGUCHI YOSHIAKI, KATO HIRONORI, NEGISHI MANABU

日本神経科学大会プログラム・抄録集 24th ( 2-3 ) 254 - 310 2001.9

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神経突起形成時のNGFによるRac1とRhoAの活性制御とそのクロストーク

YAMAGUCHI YOSHIAKI, KATO HIRONORI, NEGISHI MANABU

神経化学 40 ( 2/3 ) 310 2001.9

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NGFによるRac1の活性化・神経突起形成に対するRhoA/Rhoキナーゼの抑制作用

YAMAGUCHI YOSHIAKI, KATO HIRONORI, NEGISHI MANABU

生化学 73 ( 8 ) 863 - 863 2001.8

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三量体G蛋白質から低分子量G蛋白質へのシグナル伝達 Rho-Rhoキナーゼを介したG12ファミリーの神経突起形成調節作用

根岸学, 山口賀章, 加藤裕教

日本細胞生物学会大会講演要旨集 54回 13 - 13 2001.5

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Rho‐Rhoキナーゼを介したG12ファミリーの神経突起形成調節作用

NEGISHI MANABU, YAMAGUCHI YOSHIAKI, KATO HIRONORI

日本細胞生物学会大会講演要旨集 54th 13 2001

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G12ファミリーのRho活性化経路を介した神経機能

NEGISHI MANABU, YAMAGUCHI YOSHIAKI, KATO HIROTAKA

生化学 72 ( 8 ) 670 2000.8

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Gα12/13によるRho/Rhoキナーゼを介した神経伝達物質の遊離抑制作用

YAMAGUCHI YOSHIAKI, KATO HIRONORI, NEGISHI MANABU

生化学 72 ( 8 ) 910 - 910 2000.8

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プロスタグランジンEP3受容体によるRhoを介した神経突起の退縮を調節するシグナル伝達経路

青木純子, 加藤裕教, 山口賀章, 根岸学

生化学 71 ( 8 ) 1062 - 1062 1999.8

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三量体G蛋白質G12,G13,GqによるRhoを介した神経突起の退縮

KATO HIRONORI, AOKI JUNKO, YAMAGUCHI YOSHIAKI, YASUI SHUICHI, NEGISHI MANABU

日本神経科学大会プログラム・抄録集 22nd 289 1999.7

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Awards

平成29年度日本生化学会近畿支部奨励賞受賞

2017.5 日本生化学会近畿支部概日時計の頑強性を担う視交叉上核の分子神経シグナル

山口賀章

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平成26年度日本薬学会近畿支部奨励賞受賞

2015.1 日本薬学会近畿支部時差消失マウスの開発による概日リズムの頑強性を担う分子神経機構の解明

山口賀章

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Japan Neuroscience Society Young Investigator Award

2014.9 The Japan Neuroscience Society

YAMAGUCHI Yoshiaki

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Research Projects

Central regulation of the biological clock and extension of healthy life mediated by an orphan receptor Gpr19 and vasopressin

Grant number：22K06594 2022.4 - 2025.3

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)

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Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

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Physiological role of hypothalamic aldosterone synthase in high-salt diet-induced hypertension

Grant number：16K15119 2016

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research

Yamaguchi Yoshiaki, TAKAHASHI Hakuo, OKAMURA Hitoshi, KUROIWA Sayaka

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Authorship：Principal investigator Grant type：Competitive

Hypertension is a causative factor for ischemic heart disease, stroke, and kidney failure. Thus, its remedy is clinically important. It is widely recognized that a negative feedback mechanism of the renin - angiotensin - aldosterone system (RAAS) in the peripheral organs controls a blood pressure level; when blood pressure reaches a high level, renin secretion from the kidney is inhibited and blood pressure will be lowered. In this study, however, I found that expression of aldosterone synthase is elevated in the brain of mice fed with high salt diet. This increase is a sharp contrast with that in periphery. From this result, it is suggested that RAAS forms a positive feedback mechanism in the brain, and normalizing the activity level of RAAS in the brain is effective for treating hypertension.

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Circadian clock oscillation in the SCN

Grant number：15H01843 2015.4 - 2018.3

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A) Grant-in-Aid for Scientific Research (A)

OKAMURA HITOSHI, YAMAGUCHI YOSHIAKI, FUSTIN JEAN-MICHEL

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Grant amount：\40170000 （ Direct Cost: \30900000 、 Indirect Cost：\9270000 ）

In Drosophila, it was elucidated that the transcription and translation feedback loop of the clock gene causes a circadian rhythm with a period of about 24 hours, and it won the 2017 Nobel Prize in Medicine and Physiology. We cloned mammalian Per gene in 1997, and clarified that the circadian oscillation was not generated simply clock genes by themselves, but needs intercellular neurotransmission among clock oscillating cells. In this research project, we identified GPR176-cAMP system as a key system to generate the rhythm, mathematical model of jet lag, alternative splicing of Ck1d gene for determining period length, mammalian calcitonin receptor in temperature regulation during nap, and role of Per for the formation of polyploidization.

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Molecular and neural mechanisms underlying the robustness of the circadian clock and an approach to jet-lag-related diseases.

Grant number：15H05642 2015 - 2018

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (A) Grant-in-Aid for Young Scientists (A)

YAMAGUCHI Yoshiaki, OKAMURA Hitoshi

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Grant amount：\6760000 （ Direct Cost: \5200000 、 Indirect Cost：\1560000 ）

Almost all organisms on Earth have an internal biological clock, the circadian clock. This clock drives stable oscillations in metabolism, physiology, and behavior with a period of approximately 24 h. In mammals, circadian rhythms are generated by a timing system comprised of a master pacemaker located in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. We previously reported that arginine vasopressin receptor V1a and V1b regulate the speed of re-entrainment after abrupt light/dark advance. Here, we succeeded in real-time monitoring of Per1 and Per2 transcription separately by detecting the bioluminescence of luciferase reporters using a plastic optical fiber inserted into the SCN of freely moving rats. We also presented a new theoretical concept to understand circadian clock disruption and slow recovery from jet lag based on the mathematical model. Finally, we found that rapidly entrainable V1aV1b double knockout mice showed lower mortality under a chronic jet lag.

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In vivo real-time recording of circadian Per1 and Per2 expression in the rat suprachiasmatic nucleus

Grant number：15K12776 2015

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research

Yamaguchi Yoshiaki

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Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）

In a variety of neuroscience research fields, in vivo real-time monitoring of gene activity in the brains of freely behaving animals offers a challenging issue. Circadian gene expression in the neurons of the suprachiasmatic nucleus (SCN), a bilateral and small nucleus in the hypothalamus, is reflected in locomotor activity. Intracellularly oscillating gene expression is generated by a negative transcription-translation feedback loop by clock genes including two representative oscillatory genes, Per1 and Per2. In this study, we have succeeded in real-time monitoring of Per1 and Per2 transcription separately by detecting the bioluminescence of luciferase (luc) reporters using a plastic optical fiber inserted into the SCN of freely moving rats. Studies of in vivo transcriptional states of clock genes in freely moving animals should improve our understanding of how clock gene expression is reflected in behavioral rhythm.

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時差時における脳内時間環境の恒常性を担う神経分子メカニズムの解明

Grant number：26111710 2014 - 2015

文部科学省科学研究費補助金(新学術領域研究(研究領域提案型)) 新学術領域研究(研究領域提案型)

山口賀章

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\9360000 （ Direct Cost: \7200000 、 Indirect Cost：\2160000 ）

コルチゾルといったホルモン分泌など、私達の生理現象には24時間周期のリズムがある。この概日リズムを制御する中枢は、脳の視交叉上核（SCN）である。SCNは、全身の時間制御網により、個体として安定した時間相を構築しているとされるが、その分子神経メカニズムはほとんど解明されていない。本研究課題は、「時差」により、脳内時間恒常性のロバストネスを担うシグナルを解明することを目的としている。近年、私達は、Vasopressinの受容体であるV1aおよびV1bのダブルノックアウトマウス (V1aV1bDKOマウス) が、時差を全く示さないことを見出した（Science, 342: 85-90, 2013）。野生型マウスを時差環境下におくと、SCNの恒常性が破綻し時計遺伝子の振動リズムが消失したが、V1aV1bDKOマウスでは、瞬時にSCNのリズムが回復した。しかしながら、SCNにおける V1aとV1bの機能は未だよくわかっていない。そこで私達は、レポーターマウスからSCNを取り出し、SCNスライス培養下にて、SCN細胞の概日振動をリアルタイムで測定した。野生型マウスのSCNでは、各細胞の概日振動のピーク位相に8時間程度の位相差があるが、V1aV1bDKOマウスのSCN細胞間では、この位相差が小さくなっていた。また、野生型マウスのSCNスライスを用いて薬理学実験を行ったところ、V1aとV1bに対するアンタゴニストを投与した場合に、SCN細胞間の位相差が有意に小さくなった。したがって、SCN細胞間の位相差を8時間程度に保つことが、SCNの時間恒常性に寄与していると考えられる。

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Elucidation of the molecular and neural mechanisms of jet lag for the life style-related diseases under chronic jet lag using non-jet-lag mice

Grant number：26670027 2014

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research

YAMAGUCHI Yoshiaki

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\3770000 （ Direct Cost: \2900000 、 Indirect Cost：\870000 ）

The endogenous circadian clock drives daily oscillations in physiology and behavior. We are not usually aware of this system because it is completely synchronized with environmental light-dark cycles, but travelling rapidly across multiple time zones suddenly makes us aware of the desynchrony, causing sleep disturbances. Repeated jet-lag exposure increases the risk of lifestyle-related diseases, such as cardiovascular complaints. Especially, shiftworkers, who chronically experience jet lag socially due to rotated work-time schedules, have been shown to have a high risk in not only mental diseases but also cancer, diabetes, and obesity. However, little is known about the molecular and neural mechanisms of jet lag. We have recently revealed that mice genetically deficient in vasopressin V1a and V1b receptors are resistant to jet lag. Thus, our aim is to elucidate the fundamental mechanisms about jet lag and develop a remedy for shiftwork-related problems using non-jet-lag mice.

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SCN-Gene-Project: Molecular analysis of biological rhythms

Grant number：24240058 2012.4 - 2015.3

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A) Grant-in-Aid for Scientific Research (A)

OKAMURA Hitoshi, YAMAGUCHI Yoshiaki

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Grant amount：\47060000 （ Direct Cost: \36200000 、 Indirect Cost：\10860000 ）

Suprachiasmatic nucleus (SCN) is a center of biological rhythm. SCN emits a powerful circadian rhythm signals to other brain regions and various peripheral organs, and synchronizes systemic clocks in order of the central clock. We started SCN-Gene Project, in which genes expressed in SCN were identified histochemically, and were characterized in rhythms by making their knockout mice. By the SCN-Gene Project, we so far identified animals with longer period length, or with stronger reaction to light pulse in the night. Moreover, we isolated mice without jet lag: they abruptly change their behavioral rhythms when they are exposed to new light-dark cycles. Many of these genes, were not directly related to circadian transcription, but directly linked to intercellular or intracellular signal transductions. These findings suggest that posttranscriptional processes are strongly involved to characterize the nature of the clock.

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An elucidation of hierarchy of a biological clock and a rhythm adjustment drug by generating a novel clock function-deficient mouse

Grant number：23590107 2011 - 2013

Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(基盤研究(C)) 基盤研究(C)

Yoshiaki YAMAGUCHI

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\5460000 （ Direct Cost: \4200000 、 Indirect Cost：\1260000 ）

The endogenous circadian clock drives oscillations in physiology and behavior with a period of about 24 hours. When travelling rapidly across multiple time zones (jet lag), we become aware of the desynchrony between our internal clock and external light-dark cycle. Although jet lag is recognized as a chronobiological problem, its specific molecular and cellular mechanisms are poorly understood.In this study, we show that circadian rhythms of locomotor activity, clock gene expression, and body temperature rapidly re-entrained to phase-shifted light-dark cycles in mice genetically deficient in V1a and V1b receptors (V1aV1bDKO). Real-time imaging of cellular rhythms in the suprachiasmatic nucleus (SCN) slices suggested that interneuronal communication mediated by V1a and V1b confers on the SCN an intrinsic resistance to external rhythm perturbation. Pharmacological blockade of V1a and V1b in the SCN of wild-type mice accelerated the speed of recovery from jet lag.

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Physiological role of SCN micro-circuit on circadian clock

Grant number：21790073 2009 - 2010

Ministry of Education, Culture, Sports, Science and Technology Grants-in-Aid for Scientific Research(若手研究(B)) 若手研究(B)

Yoshiaki YAMAGUCHI

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\4420000 （ Direct Cost: \3400000 、 Indirect Cost：\1020000 ）

The glutamatergic neurotransmission in the suprachiasmatic nucleus (SCN) plays a central role in the entrainment of the circadian rhythms to environmental light-dark cycles. Although the glutamatergic effect operating via NMDAR is well elucidated, much less is known about a role of AMPAR in circadian entrainment. Here I show that in vivo microinjection of AMPA in the SCN during the early subjective night phase-delays the behavioral rhythm. These data demonstrate that activation of AMPAR is capable of phase-shifting the circadian clock both in vivo and in vitro, and are consistent with the hypothesis that activation of AMPA receptors is a critical step in the transmission of photic information to the SCN.

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Physiological roles of suprachiasmatic nucleus

2008 - 2009

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Grant type：Competitive

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体内時計の同調機能と発振機能を担う視交叉上核内神経回路の動物個体レベルでの解明

Grant number：20890108 2008 - 2009

文部科学省科学研究費補助金(若手研究(スタートアップ)) 若手研究(スタートアップ)

山口賀章

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Authorship：Principal investigator Grant type：Competitive

Grant amount：\3302000 （ Direct Cost: \2540000 、 Indirect Cost：\762000 ）

46億年間、地球は自転し昼と夜を生み出し続けた。その結果、生物は約24時間の概日リズム、体内時計を獲得した。私達はこの体内時計のおかげで睡眠、血圧、体温、食餌のリズムをコントロールできる。体内時計の中枢は脳の視交叉上核(suprachiasmatic nucleus: SCN)であり、SCNは「同調機能」と「発振機能」を持つ。SCNは機能形態学的に腹外側部(VL)と背内側部(DM)に分けられるが、これらの領域が同調機能と発振機能においてどのような役割を担っているかはほとんど不明である。今回、私自身が開発した哺乳類動物の神経細胞を動物が生きたままの状態で繰り返し不活性化できるアラトスタチン法を用いて、SCNのVL及びDM各領域の体内時計の生理的役割を動物個体レベルでの解明を試みた。まず、アラトスタチン受容体(AlstR)をDMあるいはVL領域に発現させる方法の検討を行った。そこで、EGFPを発現するAAVを作製し、マウスSCNのスライス培養に感染させたところ、SCNのほとんどの神経細胞がEGFPを発現することを確認した。現在は、DM領域あるいは、VL領域に特異的なプロモーターを用いてAlstRを発現するウイルスを作製し、各領域の神経細胞にのみ特異的にAlstRを発現させる方法を検討中である。

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Molecular Clocks to Biological Rhythms

Grant number：18002016 2006 - 2010

Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Specially Promoted Research Grant-in-Aid for Specially Promoted Research

OKAMURA Hitoshi, EMOTO Noriaki, MASUBUCHI Satoru, DOI Masao, IIGO Masayuki, NAKAHARA Daiichiro, NAKAO Kazuki, YAMAGUCHI Yoshiaki, MATSUO Masahiro

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Grant amount：\580580000 （ Direct Cost: \446600000 、 Indirect Cost：\133980000 ）

The discovery of clock genes at 1997 and the following study of the molecular machinery of clock genes, have enabled “biological time” as a research object. We begin the present study as a project of post-cloning age. We clarified the G-protein mediated novel cellular communications in the suprachiasmatic nucleus. We synthesized an artificial transcriptional factor regulating the clock gene transcriptions. We also clarified a timing mechanism of nucleic acid metabolism in the liver, miturition rhythm in the urinary bladder, and further, we identified a novel steroid synthetic enzyme, which links between circadian clock and hypertension, in the adrenal gland.

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三量体Gタンパク質G12ファミリーによる神経機能調節の研究

Grant number：01J03814 2001 - 2003

日本学術振興会科学研究費助成事業特別研究員奨励費特別研究員奨励費

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Grant amount：\3000000 （ Direct Cost: \3000000 ）

Gα12/13の新規活性測定法の開発と、Gα12/13のレセプターとの共役の特異性決定因子の解明
私は、2002年にセリンスレオニンフォスファターゼ5(PP5)が三量体Gタンパク質G12ファミリーの新規エフェクターであることを見いだした。2003年に私はPP5のTPRドメインが活性型Gα12/13と特異的に結合するという特性を利用して、TPRドメインによるpull-downにより、Gα12/13の活性を測定する新規活性測定法を開発した。
Gα12とGα13は、下流でRhoという共通の分子を利用する一方、上流のレセプターとの共役に関しては、それぞれに特異性があることが、Gα12/13のドミナントネガティヴ体を用いて示されていた。そこで、私は上記の新規アッセイ法を用いてthrombin及びLPAがGα12及びGα13を、それぞれ特異的に活性化すること、及びこの特異性が、Gα12/13のN末端アミノ酸配列の差に起因することを解明した。近年、神経細胞において、Gα12は細胞体、Gα13はneuropilと局在が異なることが報告された。このことから、Gα12/13とレセプターの細胞内局在の違いが、それらの共役及びシグナリングに重要であると考えられる。

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