title: Disruption of behavioral circadian rhythms induced by psychophysiological stress affects plasma free amino acid profiles without affecting peripheral clock gene expression in mice.
abstract: Disordered circadian rhythms are associated with various psychiatric conditions and metabolic diseases. We recently established a mouse model of a psychophysiological stress-induced chronic sleep disorder (CSD) characterized by reduced amplitude of circadian wheel-running activity and sleep-wake cycles, sleep fragmentation and hyperphagia. Here, we evaluate day-night fluctuations in plasma concentrations of free amino acids (FAA), appetite hormones and prolactin as well as the hepatic expression of circadian clock-related genes in mice with CSD (CSD mice). Nocturnal increases in wheel-running activity and circadian rhythms of plasma prolactin concentrations were significantly disrupted in CSD mice. Hyperphagia with a decreased leptin/ghrelin ratio was found in CSD mice. Day-night fluctuations in plasma FAA contents were severely disrupted without affecting total FAA levels in CSD mice. Nocturnal increases in branched-chain amino acids such as Ile, Leu, and Val were further augmented in CSD mice, while daytime increases in Gly, Ala, Ser, Thr, Lys, Arg, His, Tyr, Met, Cys, Glu, and Asn were significantly attenuated. Importantly, the circadian expression of hepatic clock genes was completely unaffected in CSD mice. These findings suggest that circadian clock gene expression does not always reflect disordered behavior and sleep rhythms and that plasma FFA profiles could serve as a potential biomarker of circadian rhythm disorders.
authors: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan; Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan. Electronic address: k-ooishi@aist.go.jp.
authors: Katsutaka
authors: K
authors: Oishi
authors: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors: Saori
authors: S
authors: Yamamoto
authors: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors: Nanako
authors: N
authors: Itoh
authors: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors: Koyomi
authors: K
authors: Miyazaki
authors: Bio-Interface Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
authors: Tadashi
authors: T
authors: Nemoto
authors: Frontier Laboratories of Value Creation, Sapporo Breweries Ltd., Yaizu, Shizuoka, Japan.
authors: Yasukazu
authors: Y
authors: Nakakita
authors: Corporate Planning Department, Sapporo Holdings Ltd., Shibuya-ku, Tokyo, Japan.
authors: Hirotaka
authors: H
authors: Kaneda
mesh_terms: D000596:Amino Acids / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D056926:CLOCK Proteins / Q000378:metabolism*; D002940:Circadian Rhythm; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D020178:Sleep Disorders, Circadian Rhythm / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D056926:CLOCK Proteins
keywords: Chronodisruption; Circadian rhythm; Clock gene; Oxidative stress; Plasma amino acid; Sleep disorder