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Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat
Philippe Aubert1,2, Elena Oleynikova1,2, Hina Rizvi1,2
1The Enteric Nervous System in Gut and Brain Disorders, INSERM, Université de Nantes, Nantes, France.
Insights
Maternal protein restriction in early life leads to gastrointestinal (GI) dysfunction and altered enteric nervous system (ENS) development in rat offspring. This may involve increased corticosteronemia, impacting gut response to stress.
Area of Science:
- Neuroscience
- Gastroenterology
- Developmental Biology
Background:
- Early-life adversity, such as maternal protein restriction (MPR), is a significant risk factor for later-life diseases.
- The impact of MPR on the gastrointestinal (GI) tract and its associated enteric nervous system (ENS) is not well understood.
Purpose of the Study:
- To investigate the effects of MPR on GI function and ENS in rat offspring.
- To assess the role of corticosteronemia and autophagy in MPR-induced alterations.
Main Methods:
- Utilized a rat model to study offspring at postnatal day 35 under basal and stress conditions (water avoidance stress - WAS).
- Assessed colonic motility, permeability, corticosteronemia, and ENS neurochemistry (ChAT-IR neurons, autophagy levels).
- Examined corticosterone effects on ENS cultures and the role of autophagy inhibition.
Main Results:
- MPR rats showed increased colonic motility, permeability, and baseline corticosteronemia compared to controls.
- MPR rats exhibited a blunted corticosteronemic and functional response to WAS.
- MPR offspring had more choline acetyltransferase-immunoreactive (ChAT-IR) neurons and reduced autophagy in myenteric neurons, findings replicated by corticosterone treatment in vitro.
Conclusions:
- MPR induces significant GI dysfunction and ENS remodeling in rat offspring.
- Elevated corticosteronemia in MPR offspring may contribute to ENS changes and altered gut stress responsiveness.
- Autophagy inhibition in enteric neurons increases vulnerability to cellular stress, suggesting a potential mechanism in MPR-induced pathology.
Abstract:
Early-life adversity is a major risk factor for the development of diseases later in life. Maternal protein restriction (MPR) is associated with morbidities in offspring affecting multiple organs, but its impact on the gastrointestinal (GI) tract remains poorly studied. Using a rat model, we examined the consequences of MPR on GI function and on the enteric nervous system (ENS) in the offspring at postnatal d 35 under basal state and following a water avoidance stress (WAS). Compared with control rats, MPR rats exhibited greater colonic motility, permeability, and corticosteronemia. In contrast to controls, MPR rats presented a blunted functional and corticosteronemic response to WAS. Furthermore, MPR rats showed an increased proportion of choline acetyltransferase-immunoreactive (ChAT-IR) neurons and a reduced level of autophagy in colonic myenteric neurons. In ENS cultures, corticosterone treatment increased the proportion of ChAT-IR neurons and reduced autophagy level in enteric neurons. Inhibition of autophagy in ENS cultures resulted in a higher vulnerability of enteric neurons to a cellular stress. Altogether, this study suggests that MPR induced GI dysfunction and ENS alterations in offspring rats and that MPR-induced increased corticosteronemia might be involved in ENS remodeling and altered responsiveness of the gut to stressors later in life.-Aubert, P., Oleynikova, E., Rizvi, H., Ndjim, M., Le Berre-Scoul, C., Grohard, P. A., Chevalier, J., Segain, J.-P., Le Drean, G., Neunlist, M., Boudin, H. Maternal protein restriction induces gastrointestinal dysfunction and enteric nervous system remodeling in rat offspring.
