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Article ; Online: Long days restore regular estrous cyclicity in mice lacking circadian rhythms

Takahiro J. Nakamura / Nana N. Takasu / Sayuri Sakazume / Yu Matsumoto / Natsuko Kawano / Julie S. Pendergast / Shin Yamazaki / Wataru Nakamura

Heliyon, Vol 9, Iss 6, Pp e16970- (2023)

2023

Abstract: Many female mammals have recurring cycles of ovulation and sexual behaviors that are regulated by reproductive hormones and confer reproductive success. In addition to sexual behaviors, circadian behavioral rhythms of locomotor activity also fluctuate ... ...

Abstract	Many female mammals have recurring cycles of ovulation and sexual behaviors that are regulated by reproductive hormones and confer reproductive success. In addition to sexual behaviors, circadian behavioral rhythms of locomotor activity also fluctuate across the estrous cycle in rodents. Moreover, there is a bidirectional relationship between circadian rhythms and estrous cyclicity since mice with disrupted circadian rhythms also have compromised estrous cycles resulting in fewer pregnancies. In the present study, we assessed whether extending day length, which alters circadian rhythms, normalizes estrous cyclicity in mice. We found that Period (Per) 1/2/3 triple knockout (KO) mice, that have disabled canonical molecular circadian clocks, have markedly disrupted estrous cycles. Surprisingly, extending the day length by only 2 h per day restored regular 4- or 5-day estrous cycles to Per1/2/3 KO mice. Longer days also induced consistent 4-day, rather than 5-day, estrous cycles in wild-type C57BL/6J mice. These data demonstrate that extending daytime light exposure could be used for enhancing reproductive success.
Keywords	Breeding efficiency ; Clock gene ; C57BL/6J mice ; Photoperiod ; Seasonal breeder ; Wheel-running ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modeling circadian regulation of ovulation timing

Takayuki Ohara / Takahiro J. Nakamura / Wataru Nakamura / Isao T. Tokuda

Scientific Reports, Vol 10, Iss 1, Pp 1-

age-related disruption of estrous cyclicity

2020 Volume 15

Abstract: Abstract The circadian clocks within the hypothalamic–pituitary–gonadal axis control estrous cycles in female rodents. The suprachiasmatic nucleus (SCN), where the central clock is located, generates daily signals to trigger surge release of luteinizing ... ...

Abstract	Abstract The circadian clocks within the hypothalamic–pituitary–gonadal axis control estrous cycles in female rodents. The suprachiasmatic nucleus (SCN), where the central clock is located, generates daily signals to trigger surge release of luteinizing hormone (LH), which in turn induces ovulation. It has been observed in aged rodents that output from the SCN such as neuronal firing activity is declined, and estrous cycles become irregular and finally stop. Circadian clock mutants display accelerated reproductive aging, suggesting the complicated interplay between the circadian system and the endocrine system. To investigate such circadian regulation of estrous cycles, we construct a mathematical model that describes dynamics of key hormones such as LH and of circadian clocks in the SCN and in the ovary, and simulate estrous cycles for various parameter values. Our simulation results demonstrate that reduction of the amplitude of the SCN signal, which is a symptom of aging, makes estrous cycles irregular. We also show that variation in the phase of the SCN signal and changes in the period of ovarian circadian clocks exacerbates the aging effect on estrous cyclicity. Our study suggests that misalignment between the SCN and ovarian circadian oscillations is one of the primary causes of the irregular estrous cycles.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparing pentafecta outcomes between nerve sparing and non nerve sparing robot-assisted radical prostatectomy in a propensity score-matched study

Tanan Bejrananda / Kiyoshi Takahara / Dutsadee Sowanthip / Tomonari Motonaga / Kota Yagi / Wataru Nakamura / Masanobu Saruta / Takuhisa Nukaya / Masashi Takenaka / Kenji Zennami / Manabu Ichino / Hitomi Sasaki / Makoto Sumitomo / Ryoichi Shiroki

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 10

Abstract: Abstract Pentafecta (continence, potency, cancer control, free surgical margins, and no complications) is an important outcome of prostatectomy. Our objective was to assess the pentafecta achievement between nerve-spring and non-nerve-sparing robot- ... ...

Abstract	Abstract Pentafecta (continence, potency, cancer control, free surgical margins, and no complications) is an important outcome of prostatectomy. Our objective was to assess the pentafecta achievement between nerve-spring and non-nerve-sparing robot-assisted radical prostatectomy (RARP) in a large single-center cohort. The study included 1674 patients treated with RARP between August 2009 and November 2022 to assess the clinical outcomes. Cox regression analyses were performed to evaluate the prognostic significance of RARP for pentafecta achievement, and 1:1 propensity score matching (PSM) was performed between the nerve-sparing and non-nerve-sparing to test the validity of the results. Pentafecta definition included continence, which was defined as the use of zero pads; potency, which was defined as the ability to achieve and maintain satisfactory erections or ones firm enough for sexual activity and sexual intercourse. The biochemical recurrence rate was defined as two consecutive PSA levels > 0.2 ng/mL after RARP; 90-day Clavien–Dindo complications ≤ 3a; and a negative surgical pathologic margin. The median follow-up period was 61.3 months (IQR 6–159 months). A multivariate Cox regression analysis demonstrated that pentafecta achievement was significantly associated with nerve-sparing (NS) approach (1188 patients) (OR 4.16; 95% CI 2.51–6.9), p < 0.001), unilateral nerve preservation (983 patients) (OR 3.83; 95% CI 2.31–6.37, p < 0.001) and bilateral nerve preservation (205 patients) (OR 7.43; 95% CI 4.14–13.36, p < 0.001). After propensity matching, pentafecta achievement rates in the NS (476 patients) and non-NS (476 patients) groups were 72 (15.1%) and 19 (4%), respectively. (p < 0.001). NS in RARP offers a superior advantage in pentafecta achievement compared with non-NS RARP. This validation study provides the pentafecta outcome after RARP associated with nerve-sparing in clinical practice.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Chronic methamphetamine uncovers a circadian rhythm in multiple-unit neural activity in the dorsal striatum which is independent of the suprachiasmatic nucleus

Shota Miyazaki / Yu Tahara / Christopher S. Colwell / Gene D. Block / Wataru Nakamura / Takahiro J. Nakamura

Neurobiology of Sleep and Circadian Rhythms, Vol 11, Iss , Pp 100070- (2021)

2021

Abstract: The dorsal striatum forms part of the basal ganglia circuit that is a major regulator of voluntary motor behavior. Dysfunction in this circuit is a critical factor in the pathology of neurological (Parkinson's and Huntington's disease) as well as ... ...

Abstract	The dorsal striatum forms part of the basal ganglia circuit that is a major regulator of voluntary motor behavior. Dysfunction in this circuit is a critical factor in the pathology of neurological (Parkinson's and Huntington's disease) as well as psychiatric disorders. In this study, we employed in vivo real-time monitoring of multiple unit neural activity (MUA) in the dorsal striatum of freely moving mice. We demonstrate that the striatum exhibits robust diurnal and circadian rhythms in MUA that peak in the night. These rhythms are dependent upon the central circadian clock located in the suprachiasmatic nucleus (SCN) as lesions of this structure caused the loss of rhythmicity measured in the striatum. Nonetheless, chronic treatment of methamphetamine (METH) makes circadian rhythms appear in MUA recorded from the striatum of SCN-lesioned mice. These data demonstrate that the physiological properties of neurons in the dorsal striatum are regulated by the circadian system and that METH drives circadian rhythms in striatal physiology in the absence of the SCN. The finding of SCN-driven circadian rhythms in striatal physiology has important implications for an understanding of the temporal regulation of motor control as well as revealing how disease processes may disrupt this regulation.
Keywords	Circadian rhythm ; Dopamine ; Methamphetamine ; Multiple unit neural activity ; Striatum ; Suprachiasmatic nucleus ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571 ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A simple method using ex vivo culture of hair follicle tissue to investigate intrinsic circadian characteristics in humans

Ai Yamaguchi / Ritsuko Matsumura / Takashi Matsuzaki / Wataru Nakamura / Koichi Node / Makoto Akashi

Scientific Reports, Vol 7, Iss 1, Pp 1-

2017 Volume 11

Abstract: Abstract Almost all organisms maintain a circadian clock from birth to death to synchronize their own physiology and behavior with the earth’s rotation. Because the in vivo evaluation of human circadian characteristics is labor-intensive, in vitro or ex ... ...

Abstract	Abstract Almost all organisms maintain a circadian clock from birth to death to synchronize their own physiology and behavior with the earth’s rotation. Because the in vivo evaluation of human circadian characteristics is labor-intensive, in vitro or ex vivo approaches could provide advantages. In this study, to enable the simple and non-invasive evaluation of autonomous circadian oscillation, we established a method for monitoring clock gene expression by performing ex vivo culture of whole hair root tissue. This method is extremely simple and imposes little burden on subjects. Results obtained using Cryptochrome-deficient mice support that circadian period length in hair tissue correlates with intrinsic period length observed in physiology and behavior. We then applied this method to old-old subjects with severe dementia, who showed abnormal circadian behavior, and found that their peripheral clocks autonomously oscillated in a manner similar to those of healthy or younger subjects, indicating that the effect of cellular senescence on the autonomous clock oscillator is limited at least in some cell types. Although further validation may be required, the hair tissue-based culture assay would be a tool to investigate intrinsic circadian characteristics in humans.
Keywords	Medicine ; R ; Science ; Q
Subject code	571
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Seafloor observations indicate spatial separation of coseismic and postseismic slips in the 2011 Tohoku earthquake

Takeshi Iinuma / Ryota Hino / Naoki Uchida / Wataru Nakamura / Motoyuki Kido / Yukihito Osada / Satoshi Miura

Nature Communications, Vol 7, Iss 1, Pp 1-

2016 Volume 9

Abstract: Postseismic slip of the 2011 Tohoku earthquake in Japan has occurred on the plate interface, but quantifying the slip has been difficult due to a lack of seafloor data. Here, the authors use seafloor and terrestrial data and show that areas of co- and ... ...

Abstract	Postseismic slip of the 2011 Tohoku earthquake in Japan has occurred on the plate interface, but quantifying the slip has been difficult due to a lack of seafloor data. Here, the authors use seafloor and terrestrial data and show that areas of co- and postseismic slip are spatially separated.
Keywords	Science ; Q
Language	English
Publishing date	2016-11-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Polar functional group-containing glycolipid CD1d ligands modulate cytokine-biasing responses and prevent experimental colitis

Shinsuke Inuki / Natsumi Hirata / Emi Kashiwabara / Junichiro Kishi / Toshihiko Aiba / Toshiaki Teratani / Wataru Nakamura / Yoshimi Kojima / Toru Maruyama / Takanori Kanai / Yukari Fujimoto

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 12

Abstract: Abstract The MHC class I-like molecule CD1d is a nonpolymorphic antigen-presenting glycoprotein, and its ligands include glycolipids, such as α-GalCer. The complexes between CD1d and ligands activate natural killer T cells by T cell receptor recognition, ...

Abstract	Abstract The MHC class I-like molecule CD1d is a nonpolymorphic antigen-presenting glycoprotein, and its ligands include glycolipids, such as α-GalCer. The complexes between CD1d and ligands activate natural killer T cells by T cell receptor recognition, leading to the secretion of various cytokines (IFN-γ, IL-4, IL-17A, etc.). Herein, we report structure–activity relationship studies of α-GalCer derivatives containing various functional groups in their lipid acyl chains. Several derivatives have been identified as potent CD1d ligands displaying higher cytokine induction levels and/or unique cytokine polarization. The studies also indicated that flexibility of the lipid moiety can affect the binding affinity, the total cytokine production level and/or cytokine biasing. Based on our immunological evaluation and investigation of physicochemical properties, we chose bisamide- and Bz amide-containing derivatives 2 and 3, and evaluated their in vivo efficacy in a DSS-induced model of ulcerative colitis. The derivative 3 that exhibits Th2- and Th17-biasing responses, demonstrated significant protective effects against intestinal inflammation in the DSS-induced model, after a single intraperitoneal injection.
Keywords	Medicine ; R ; Science ; Q
Subject code	540
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Cell and tissue-autonomous development of the circadian clock in mouse embryos

Inada, Yutaka / Hitoshi Uchida / Yasuhiro Umemura / Wataru Nakamura / Takayoshi Sakai / Nobuya Koike / Kazuhiro Yagita

Federation of European Biochemical Societies FEBS letters. 2014 Jan. 31, v. 588, no. 3

2014

Abstract: The emergence of the circadian rhythm is a dramatic and physiologically essential event for mammals to adapt to daily environmental cycles. It has been demonstrated that circadian rhythms develop during the embryonic stage even when the maternal central ... ...

Abstract	The emergence of the circadian rhythm is a dramatic and physiologically essential event for mammals to adapt to daily environmental cycles. It has been demonstrated that circadian rhythms develop during the embryonic stage even when the maternal central pacemaker suprachiasmatic nucleus has been disrupted. However, the mechanisms controlling development of the circadian clock are not yet fully understood. Here, we show that the circadian molecular oscillation in primary dispersed embryonic cells and explanted salivary glands obtained from mPER2Luc mice embryos developed cell- or tissue-autonomously even in tissue culture conditions. Moreover, the circadian clock in the primary mPER2Luc fibroblasts could be reprogrammed by the expression of the reprogramming factors. These findings suggest that mammalian circadian clock development may interact with cellular differentiation mechanisms.
Keywords	cell differentiation ; circadian rhythm ; fibroblasts ; mice ; salivary glands ; tissue culture
Language	English
Dates of publication	2014-0131
Size	p. 459-465.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	212746-5
ISSN	1873-3468 ; 0014-5793
ISSN (online)	1873-3468
ISSN	0014-5793
DOI	10.1016/j.febslet.2013.12.007
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: In vivo monitoring of multi-unit neural activity in the suprachiasmatic nucleus reveals robust circadian rhythms in Period1⁻/⁻ mice.

Nana N Takasu / Julie S Pendergast / Cathya S Olivas / Shin Yamazaki / Wataru Nakamura

PLoS ONE, Vol 8, Iss 5, p e

2013 Volume 64333

Abstract: The master pacemaker in the suprachiasmatic nucleus (SCN) controls daily rhythms of behavior in mammals. C57BL/6J mice lacking Period1 (Per1⁻/⁻) are an anomaly because their SCN molecular rhythm is weak or absent in vitro even though their locomotor ... ...

Abstract	The master pacemaker in the suprachiasmatic nucleus (SCN) controls daily rhythms of behavior in mammals. C57BL/6J mice lacking Period1 (Per1⁻/⁻) are an anomaly because their SCN molecular rhythm is weak or absent in vitro even though their locomotor activity rhythm is robust. To resolve the contradiction between the in vitro and in vivo circadian phenotypes of Per1⁻/⁻ mice, we measured the multi-unit activity (MUA) rhythm of the SCN neuronal population in freely-behaving mice. We found that in vivo Per1⁻/⁻ SCN have high-amplitude MUA rhythms, demonstrating that the ensemble of neurons is driving robust locomotor activity in Per1⁻/⁻ mice. Since the Per1⁻/⁻ SCN electrical activity rhythm is indistinguishable from wild-types, in vivo physiological factors or coupling of the SCN to a known or unidentified circadian clock(s) may compensate for weak endogenous molecular rhythms in Per1⁻/⁻ SCN. Consistent with the behavioral light responsiveness of Per1⁻/⁻ mice, in vivo MUA rhythms in Per1⁻/⁻ SCN exhibited large phase shifts in response to light. Since the acute response of the MUA rhythm to light in Per1⁻/⁻ SCN is equivalent to wild-types, an unknown mechanism mediates enhanced light responsiveness of Per1⁻/⁻ mice. Thus, Per1⁻/⁻ mice are a unique model for investigating the component(s) of the in vivo environment that confers robust rhythmicity to the SCN as well as a novel mechanism of enhanced light responsiveness.
Keywords	Medicine ; R ; Science ; Q
Subject code	570
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Recovery from Age-Related Infertility under Environmental Light-Dark Cycles Adjusted to the Intrinsic Circadian Period

Nana N. Takasu / Takahiro J. Nakamura / Isao T. Tokuda / Takeshi Todo / Gene D. Block / Wataru Nakamura

Cell Reports, Vol 12, Iss 9, Pp 1407-

2015 Volume 1413

Abstract: Female reproductive function changes during aging with the estrous cycle becoming more irregular during the transition to menopause. We found that intermittent shifts of the light-dark cycle disrupted regularity of estrous cycles in middle-aged female ... ...

Abstract	Female reproductive function changes during aging with the estrous cycle becoming more irregular during the transition to menopause. We found that intermittent shifts of the light-dark cycle disrupted regularity of estrous cycles in middle-aged female mice, whose estrous cycles were regular under unperturbed 24-hr light-dark cycles. Although female mice deficient in Cry1 or Cry2, the core components of the molecular circadian clock, exhibited regular estrous cycles during youth, they showed accelerated senescence characterized by irregular and unstable estrous cycles and resultant infertility in middle age. Notably, tuning the period length of the environmental light-dark cycles closely to the endogenous one inherent in the Cry-deficient females restored the regularity of the estrous cycles and, consequently, improved fertility in middle age. These results suggest that reproductive potential can be strongly influenced by age-related changes in the circadian system and normal reproductive functioning can be rescued by the manipulation of environmental timing signals.
Keywords	Biology (General) ; QH301-705.5
Subject code	580
Language	English
Publishing date	2015-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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