title: N-Acetylmannosamine improves sleep-wake quality in middle-aged mice: relevance to autonomic nervous function.
abstract: Aging is associated with a variety of physiological changes originating peripherally and centrally, including within the autonomic nervous system. Sleep-wake disturbances constitute reliable hallmarks of aging in several animal species and humans. Recent studies have been interested in N-acetylmannosamine (ManNAc) a potential therapeutic agent for improving quality of life, as well as preventing age-related cognitive decline. In this study, ManNAc (5.0 mg/ml) was administered in the drinking water of middle-aged male C57BL/6J mice (55 weeks old) for 7 days. Mice were housed under a 12:12 h light:dark cycle at 23-24 °C. We evaluated bio-behavioral activity using electrocardiogram, body temperature and locomotor activity recorded by an implanted telemetry transmitter. To estimate sleep-wake profile, surface electroencephalogram and electromyogram leads connected to a telemetry transmitter were also implanted in mice. Autonomic nervous activity was evaluated using power spectral analysis of heart rate variability. ManNAc-treated mice spent more time in a wakeful state and less time in slow wave sleep during the dark phase. Parasympathetic nervous activity was increased following ManNAc treatment, then the sympatho-vagal balance was shifted predominance of parasympathetic nervous system. Furthermore, improvement in sleep-wake pattern was associated with increased parasympathetic nervous activity. These results suggest that ManNAc treatment can improve bio-behavioral activity and sleep-wake quality in middle-aged mice. This may have implications for improving sleep patterns in elderly humans.
authors.affiliation: Laboratory of Veterinary Pathophysiology and Animal Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan. Electronic address: akuwam@mail.ecc.u-tokyo.ac.jp.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kuwahara
authors.affiliation: Laboratory of Veterinary Pathophysiology and Animal Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ito
authors.affiliation: Laboratory of Cellular Biochemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Hayakawa
authors.affiliation: Laboratory of Cellular Biochemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Yagi
authors.affiliation: Laboratory of Cellular Biochemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Shiota
mesh_terms: D000375:Aging; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D058256:Brain Waves / Q000187:drug effects; D004562:Electrocardiography; D004569:Electroencephalography; D004576:Electromyography; D005583:Fourier Analysis; D006339:Heart Rate / Q000187:drug effects; D006595:Hexosamines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D012890:Sleep / Q000187:drug effects*; D013223:Statistics as Topic; D013686:Telemetry; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D006595:Hexosamines; C002022:N-acetylmannosamine
keywords: Aging; Autonomic nervous system; Body temperature; Heart rate; N-acetylmannosamine; Orexin; Sleep