The Effects of Chronic Unpredictable Mild Stress and Semi-Pure Diets on the Brain, Gut and Adrenal Medulla in C57BL6 Mice

Int J Mol Sci. 2023 Sep 27;24(19):14618. doi: 10.3390/ijms241914618.

Abstract

Chronic stress is known to perturb serotonergic regulation in the brain, leading to mood, learning and memory impairments and increasing the risk of developing mood disorders. The influence of the gut microbiota on serotonergic regulation in the brain has received increased attention recently, justifying the investigation of the role of diet on the gut and the brain in mood disorders. Here, using a 4-week chronic unpredictable mild stress (CUMS) model in mice, we aimed to investigate the effects of a high-fat high-glycaemic index (HFD) and high-fibre fruit & vegetable "superfood" (SUP) modifications of a semi-pure AIN93M diet on behaviour, serotonin synthesis and metabolism pathway regulation in the brain and the gut, as well as the gut microbiota and the peripheral adrenal medullary system. CUMS induced anxiety-like behaviour, dysregulated the tryptophan and serotonin metabolic pathways in the hippocampus, prefrontal cortex, and colon, and altered the composition of the gut microbiota. CUMS reduced the catecholamine synthetic capacity of the adrenal glands. Differential effects were found in these parameters in the HFD and SUP diet. Thus, dietary modifications may profoundly affect the multiple dynamic systems involved in mood disorders.

Keywords: depression; diet; gut-brain axis; microbiota; pathways; stress.

MeSH terms

  • Adrenal Medulla* / metabolism
  • Animals
  • Brain / metabolism
  • Depression / metabolism
  • Diet
  • Mice
  • Mice, Inbred C57BL
  • Serotonin* / metabolism
  • Stress, Psychological / metabolism

Substances

  • Serotonin

Grants and funding

This project was funded by the University of South Australia by providing a PhD scholarship to Mauritz Frederick Herselman and internal funding to Larisa Bobrovskaya to support PhD projects.