Untargeted metabolomics analysis of rat hippocampus subjected to sleep fragmentation

Dae Wui Yoon, Hyuk Nam Kwon, Xing Jin, Jin Kwan Kim, Seung Ku Lee, Sunghyouk Park, Chang Ho Yun, Chol Shin

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Sleep fragmentation (SF) commonly occurs in several pathologic conditions and is especially associated with impairments of hippocampus-dependent neurocognitive functions. Although the effects of SF on hippocampus in terms of protein or gene levels were examined in several studies, the impact of SF at the metabolite level has not been investigated. Thus, in this study, the differentially expressed large-scale metabolite profiles of hippocampus in a rat model of SF were investigated using untargeted metabolomics approaches. Forty-eight rats were divided into the following 4 groups: 4-day SF group, 4-day exercise control (EC) group, 15-day SF group, and 15-day EC group (n = 12, each). SF was accomplished by forced exercise using a walking wheel system with 30-s on/90-s off cycles, and EC condition was set at 10-min on/30-min off. The metabolite profiles of rat hippocampi in the SF and EC groups were analyzed using liquid chromatography/mass spectrometry. Multivariate analysis revealed distinctive metabolic profiles and marker signals between the SF and corresponding EC groups. Metabolic changes were significant only in the 15-day SF group. In the 15-day SF group, L-tryptophan, myristoylcarnitine, and palmitoylcarnitine were significantly increased, while adenosine monophosphate, hypoxanthine, L-glutamate, L-aspartate, L-methionine, and glycerophosphocholine were decreased compared to the EC group. The alanine, aspartate, and glutamate metabolism pathway was observed as the common key pathway in the 15-day SF groups. The results from this untargeted metabolomics study provide a perspective on metabolic impact of SF on the hippocampus.

Original languageEnglish
Pages (from-to)74-83
Number of pages10
JournalBrain Research Bulletin
Publication statusPublished - 2019 Nov

Bibliographical note

Funding Information:
This work was supported by the Basic Science Research Programs through National Research Foundation of Korea (NRF) funded by the Korea government (MSIT) ( NRF-2018R1A3B1052328 and 2014M3A9B6069340 ).

Publisher Copyright:
© 2019


  • Control
  • Exercise
  • Hippocampus
  • Metabolites
  • Sleep fragmentation
  • Untargeted metabolomics

ASJC Scopus subject areas

  • General Neuroscience


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