In Nantes, a team Inserm has just shown that cortisol, a hormone which participates in particular in stress management, acts directly on the plasticity of the intestinal nervous system. This phenomenon would be the cause of changes in the contractility of the intestinal muscles and transit disorders.
Diarrhea, constipation, abdominal pain…: although psychological stress is known to promote these digestive disorders, the underlying mechanisms are not fully understood. So far the role of cortisol, the “stress hormone”, has been studied very little. Still, it could be important. We know that people treated chronically by administering cortisol – because they produce no more or not enough of it, for example due to Addison’s disease or after the removal of a adrenal gland – can suffer from digestive disorders when their treatment is poorly balanced. In Nantes, Michel Neunlist and Kalyane Bach-Ngohou therefore decided to look into the relationship between stress, cortisol and digestive disorders, in the experimental mouse model. Their work is the first to suggest that cortisol directly influences the neurons that make up the enteric nervous system, a tissue independent of the central nervous systemdistributed throughout the digestive tract, which regulates gastrointestinal functions.
To induce stress and measure its impact on the mice’s digestive systems, the researchers first placed the animals for an hour on a platform floating in water. They found that the amount of stool passed by these mice was higher than that passed by their caged counterparts. They then took samples of the enteric nervous system from the animals in both groups: the tissue of the mice that had been stressed had more acetylcholine-producing neurons (cholinergic neurons), which are known to facilitate intestinal contraction. ” In order to confirm that the digestive disorders of the mice were linked to these neurons, we subjected colic muscle samples to electric currents, explique Kalyane Bach-Ngohou. The contractility of samples from stressed mice was indeed stronger. »
A change in gene expression
The researchers then looked at the cellular mechanisms at work. They showed that corticosterone – the homolog of cortisol in mice – is involved in these phenomena: “ We found that the receptor for the hormone, named GR, is present in cholinergic neurons of the enteric nervous system, both in control mice and in those that had been stressed. », Underlines Kalyane Bach-Ngohou. With one difference, however: In a normal situation, the GR receptor is mainly located in the cytoplasm cells. Under stress, corticosterone binds to the GR and the GR-corticosterone couple migrates into the cell nucleus where it activates the transcription of different genes, continues the researcher. We have shown that this process is associated with an increase in the proportion of neurons that synthesize acetylcholine in the enteric nervous system. This leads to an increase in neuromuscular cholinergic transmission, itself probably the cause of the acceleration of colonic transit observed in stressed animals. On the other hand, researchers have shown that the use of a antagonist specific for the GR receptor decreases stool emission under the effect of stress.
The team is continuing its work to determine the nature and function of genes targeted by the GR-corticosterone couple in enteric neurons, probably involved in intestinal manifestations. ” Determining the nature and function of these genes could lead us to identify new therapeutic targets and lead to new solutions to relieve people treated with cortisol who suffer from digestive disorders, linked to the difficulty of pharmacologically mimicking circadian variations of natural cortisol. , note Kalyane Bach-Ngohou. And these drugs could be offered to those who suffer from irritable bowel syndrome or other pathologies associated with high cortisol levels and digestive disorders: psychiatric, inflammatory, or nutritional diseases… ».
Kalyane Bach-Ngohou is a researcher in the Enteric Nervous System in Digestive and Brain Diseases research unit (unit 1235 Inserm/Nantes University) directed by Michel Neunlist, in Nantes.
Source : J. Blin et coll. Psychological stress induces an increase in cholinergic enteric neuromuscular pathways mediated by glucocorticoid receptors. Front Neurosci, 14 février 2023 ; DOI:10.3389/fnins.2023.1100473