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

ABSTRACT: Chronic jet lag, a model of shiftwork, increases mortality in aged mice. One potential reason for this association is that the chronic desynchronization between the internal clock phase and the environmental light/dark (LD) cycle might increase the mortality rate. However, this hypothesis has not been examined because of the lack of an appropriate animal model to prove this speculation. Here, we found that rapidly entrainable vasopressin receptor V1a-/-V1b-/- mice showed lower mortality under a chronic jet lag condition. Moreover, we found that pharmacological inactivation of V1a and V1b signaling decreased mortality even in aged wild-type mice, thus providing a potential pharmaceutical intervention for shiftwork-related health problems.

SUBMITTER: Yamaguchi Y

PROVIDER: S-EPMC6123867 | biostudies-other | 2018 Jul

REPOSITORIES: biostudies-other

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

Yamaguchi Yoshiaki Y Okamura Hitoshi H

iScience 20180718

Chronic jet lag, a model of shiftwork, increases mortality in aged mice. One potential reason for this association is that the chronic desynchronization between the internal clock phase and the environmental light/dark (LD) cycle might increase the mortality rate. However, this hypothesis has not been examined because of the lack of an appropriate animal model to prove this speculation. Here, we found that rapidly entrainable vasopressin receptor V1a<sup>-/-</sup>V1b<sup>-/-</sup> mice showed lo ...[more]

PMID: 30240642

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Project description:BackgroundEvidence suggests that circadian rhythm disorder is associated with a variety of gastrointestinal diseases, and the circadian rhythm plays a key role in maintaining the homeostasis of intestinal flora. The underlying mechanisms are still not completely identified. This study was aimed to explore whether jet lag-caused circadian disruption influences gut microbiome and its metabolites.MethodsMice were synchronized with 12-h light/dark cycles (control group) or subjected to daily 8-h advance of the light/dark cycle for every 3 days (jet-lagged group). Four months later, fecal samples and jejunal contents were collected and analyzed by 16S rRNA gene sequencing. In addition, fecal samples were subjected to metabolome analysis with ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).ResultsThe results of 16s rRNA sequencing showed that chronic jet lag led to decreased microbial abundance, richness, and diversity in both feces and jejunal contents. ANOSIM analysis revealed significant difference between control and jet-lagged groups. As the colonic microbiome, the abundance of Bacteroidetes phylum was significantly decreased and that of Actinobacteria phylum was increased in jet-lagged mice. Jet lag increased the ratio of Firmicutes to Bacteroidetes, an indicator for the imbalance of gut microbiota. Metabolome analysis of fecal samples showed that the levels of tryptophan and its derivatives were decreased in jet-lagged mice. In addition, fecal levels of secondary bile acids changed under jet lag conditions. Correlation analysis identified associations between tryptophan (and its derivatives) levels and colonic microbiota.ConclusionsThis study presents a comprehensive landscape of gut microbiota and its metabolites in mice subjected to chronic jet lag. The results suggest that circadian disruption may lead to changes in fecal and jejunal microbiota and fecal metabolites. Moreover, our results demonstrate a novel interplay between the gut microbiome and metabolome.

Dataset Information

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

Publications

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

Similar Datasets

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