Repeated early-life exposure to anaesthesia and surgery causes subsequent anxiety-like behaviour and gut microbiota dysbiosis in juvenile rats.
Br J Anaesth
; 130(2): 191-201, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-36088134
ABSTRACT
BACKGROUND:
Early exposure to general anaesthetics for multiple surgeries or procedures might negatively affect brain development. Recent studies indicate the importance of microbiota in the development of stress-related behaviours. We determined whether repeated anaesthesia and surgery in early life cause gut microbiota dysbiosis and anxiety-like behaviours in rats.METHODS:
Sprague Dawley rats received skin incisions under sevoflurane 2.3 vol% three times during the first week of life. After 4 weeks, gut microbiota, anxiety-related behaviours, hippocampal serotonergic activity, and plasma stress hormones were tested. Subsequently, we explored the effect of faecal microbiota transplantation from multiple anaesthesia/surgery exposed rats after administration of a cocktail of antibiotics on anxiety-related behaviours.RESULTS:
Anxiety-like behaviours were observed in rats with repeated anaesthesia/surgery exposures In the OF test, multiple anaesthesia/surgery exposures induced a decrease in the time spent in the centre compared to the Control group (P<0.05, t=3.05, df=16, Cohen's d=1.44, effect size=0.58). In the EPM test, rats in Multiple AS group travelled less (P<0.05, t=5.09, df=16, Cohen's d=2.40, effective size=0.77) and spent less time (P<0.05, t=3.58, df=16, Cohen's d=1.69, effect size=0.65) in the open arms when compared to the Control group. Repeated exposure caused severe gut microbiota dysbiosis, with exaggerated stress response (P<0.01, t=4.048, df=16, Cohen's d=-1.91, effect size=-0.69), a significant increase in the hippocampal concentration of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) (P<0.05; for 5-HT t=3.33, df=18, Cohen's d=-1.49, effect size=-0.60; for 5-HIAA t=3.12, df=18, Cohen's d=-1.40, effect size=-0.57), and changes in gene expression of serotonergic receptors later in life (for Htr1a P<0.001, t=4.49, df=16, Cohen's d=2.24, effect size=0.75; for Htr2c P<0.01, t=3.72, df=16, Cohen's d=1.86, effect size=0.68; for Htr6 P<0.001, t=7.76, df=16, Cohen's d=3.88, effect size=0.89). Faecal microbiota transplantation led to similar anxiety-like behaviours and changes in the levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid.CONCLUSIONS:
Gut microbiota dysbiosis caused by early repeated exposure to anaesthesia and surgery affects long-term anxiety emotion behaviours in rats.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Microbioma Gastrointestinal
/
Anestesia
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article