The Open Biochemistry Journal

ISSN: 1874-091X ― Volume 14, 2020

The Clock Genes Are Involved in The Deterioration of Atopic Dermatitis after Day-and-Night Reversed Physical Stress in NC/Nga Mice

Keiichi Hiramoto1, *, Kumi Orita2, Yurika Yamate1, Emiko Kasahara3, Satoshi Yokoyama4, Eisuke F. Sato
1 Department of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3 Minamitamagakicho, Suzuka, Mie513-8670, Japan
2 Department of Orthopedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka545-8585, Japan
3 Department of Pharmaceutical Sciences, Osaka University Graduate School, 1-6 Yamadaoka, Suita, Osaka565-0871, Japan
4 Department of Pharmaceutical Sciences, Gifu Pharmaceutical University, 1-25-4 Daigakunishi, Gifu501-1196, Japan



In modern society, irregular lifestyles are a problem. It is well known that Atopic Dermatitis (AD) occurs during physical stress in people with an irregular lifestyle. We evaluated the influence that day-and-night reversal physical stress has on AD.


Six-week-old specific-pathogen-free and conventional NC/Nga male mice were used. For the day-and-night reversal procedure, the mice ran on a treadmill at a slow speed of 10 m/min for 12 h (between 8:00 and 20:00). Then, between 20:00 and 8:00, we put the mice in a dark place. This treatment was repeated every day for two weeks. The behavioral circadian rhythm of the mice was evaluated with the open field test. Then, the mice were sacrificed and histological examinations of the tissues, the expression of peptide hormones, corticosterone, Immunoglobulin E, histamine, and cytokines was performed using an enzyme-linked immunosorbent assay.


In the treadmill-treated conventional NC/Nga mice, AD symptoms were deteriorated compared with the non-treated conventional NC/Nga mice. The levels of Period (Per) 2, Clock, and brain and muscle arnt-like protein 1 (Bmal1) in the skin were increased constantly in the treadmill-treated conventional mice. Furthermore, the expression of Retinoic Acid-related Orphan Receptor (ROR)α, which activates Bmal1, was increased in the treadmill-treated conventional mice compared with the non-treated conventional mice. In addition, when non-treated conventional mice were administrated by the agonist of RORα, AD symptoms were deteriorated similar to treadmill-treated conventional mice.


In the day-and-night reversal mice, the clock genes were increased constantly, indicating that this is a factor that deteriorated AD.

Keywords: Atopic dermatitis, Period 2, Clock, Brain and muscle arnt-like protein 1, Retinoic acid-related orphan receptor α, Day-and-night reversal physical stress .

Article Information

Identifiers and Pagination:

Year: 2018
Volume: 12
First Page: 87
Last Page: 102
Publisher Id: TOBIOCJ-12-87
DOI: 10.2174/1874091X01812010087

Article History:

Received Date: 15/03/2018
Revision Received Date: 05/06/2018
Acceptance Date: 8/6/2018
Electronic publication date: 29/06/2018
Collection year: 2018

© 2018 Hiramoto et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Pharmaceutical Science, Suzuka University of Medical Science, 3500-3 Minamitamagakicho, Suzuka, Mie 513-8670, Japan, Tel: +81-59-340-0575, Fax: +81-59-368-1271, E-mail:

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