Ozone rectal insufflation mitigates chronic rapid eye movement sleep deprivation-induced cognitive impairment through inflammation alleviation and gut microbiota regulation in mice

Med Gas Res. 2024 Dec 1;14(4):213-224. doi: 10.4103/mgr.MEDGASRES-D-23-00036. Epub 2024 Mar 28.

Abstract

A range of sleep disorders has the potential to adversely affect cognitive function. This study was undertaken with the objective of investigating the effects of ozone rectal insufflation (O3-RI) on cognitive dysfunction induced by chronic REM sleep deprivation, as well as elucidating possible underlying mechanisms. O3-RI ameliorated cognitive dysfunction in chronic REM sleep deprived mice, improved the neuronal damage in the hippocampus region and decreased neuronal loss. Administration of O3-RI may protect against chronic REM sleep deprivation induced cognitive dysfunction by reversing the abnormal expression of Occludin and leucine-rich repeat and pyrin domain-containing protein 3 inflammasome as well as interleukin-1β in the hippocampus and colon tissues. Moreover, the microbiota diversity and composition of sleep deprivation mice were significantly affected by O3-RI intervention, as evidenced by the reversal of the Firmicutes/Bacteroidetes abundance ratio and the relative abundance of the Bacteroides genus. In particular, the relative abundance of the Bacteroides genus demonstrated a pronounced correlation with cognitive impairment and inflammation. Our findings suggested that O3-RI can improve cognitive dysfunction in sleep deprivation mice, and its mechanisms may be related to regulating gut microbiota and alleviating inflammation and damage in the hippocampus and colon.

MeSH terms

  • Animals
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / etiology
  • Gastrointestinal Microbiome* / drug effects
  • Hippocampus* / metabolism
  • Inflammasomes / metabolism
  • Inflammation*
  • Interleukin-1beta / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Occludin / metabolism
  • Ozone* / administration & dosage
  • Ozone* / pharmacology
  • Rectum
  • Sleep Deprivation* / complications
  • Sleep, REM

Substances

  • Ozone
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Interleukin-1beta
  • Occludin
  • Inflammasomes
  • Nlrp3 protein, mouse

Grants and funding

Funding: This study was supported by the National Natural Science Foundation of China, No. 82072086.