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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Neonatal hyperoxia induces gut dysbiosis and behavioral changes in adolescent mice
Yu-Chun Lo1, Kai-Yun Chen1, Hsiu-Chu Chou2
1The Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC.
Insights
Neonatal hyperoxia in mice disrupted gut microbiota and reduced brain myelination, leading to social and motor deficits in adolescence. This highlights potential long-term impacts of early-life oxygen exposure.
Area of Science:
- Neuroscience
- Microbiology
- Developmental Biology
Background:
- Supplemental oxygen therapy is common for preterm infants with respiratory issues.
- Neonatal hyperoxia is known to disrupt intestinal and brain development, including plasticity and myelination.
- The link between neonatal hyperoxia, gut microbiota changes, and behavioral outcomes remains unclear.
Purpose of the Study:
- To investigate the long-term effects of neonatal hyperoxia on gut microbiota composition and brain development.
- To assess the impact of early-life hyperoxia on social behavior and motor coordination in adolescent mice.
- To explore the potential association between gut dysbiosis, altered brain myelination, and behavioral deficits.
Main Methods:
- C57BL/6 mouse pups were exposed to hyperoxia (85% O2) or room air (RA) from postnatal days 1-7.
- Mice were subsequently reared in RA, with intestinal microbiota sampled on days 7 and 42.
- Behavioral tests and brain tissue analysis for myelination and apoptosis were conducted on day 42.
Main Results:
- Neonatal hyperoxia altered gut microbiota, decreasing tight junction proteins and increasing Proteobacteria and Epsilonbacteraeota.
- Hyperoxia-exposed mice showed reduced sociability, impaired motor coordination, decreased brain myelination, and increased apoptosis.
- These deficits were observed in adolescent mice following early-life hyperoxia exposure.
Conclusions:
- Neonatal hyperoxia significantly alters gut microbiota composition and diversity.
- Early-life hyperoxia exposure leads to reduced brain myelination and increased neuronal apoptosis.
- These physiological changes are associated with social interaction deficits and impaired motor coordination in adolescent mice.
Background:
Supplemental oxygen is often required to treat preterm infants with respiratory disorders. Experimental studies have demonstrated that hyperoxia results in the disruption of intestinal and neuronal plasticity and myelination of the brain. The association between the neonatal hyperoxia and changes of phenotypes in gut microbiota and in behaviors is not clear to date.
Methods:
We designed an animal experiment that C57BL/6 mice pups were reared in either room air (RA) or hyperoxia (85% O2) from postnatal days 1 to 7. From postnatal days 8 to 42, the mice were reared in RA. Intestinal microbiota was sampled from the lower gastrointestinal tract on postnatal days 7 and 42, and behavioral tests were performed and brain tissues were collected on postnatal day 42.
Results:
Neonatal hyperoxia decreased intestinal tight junction protein expression and altered intestinal bacterial composition and diversity on postnatal day 7. Among the concrete discriminative features, Proteobacteria and Epsilonbacteraeota were significantly elevated in hyperoxia-reared mice on postnatal days 7 and 42, respectively. Hyperoxia-reared mice exhibited significantly reduced sociability and interest in social novelty and impaired motor coordination compared with RA-reared mice on postnatal day 42. Hyperoxia-reared mice also exhibited significantly reduced myelination and a significantly higher number of apoptotic cells in the brain compared with RA-reared mice on postnatal day 42.
Conclusion:
Neonatal hyperoxia during the first week of life altered gut microbiota and reduced brain myelination that might associate with the deficits of social interaction and motor coordination in adolescent mice.
