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Neurochemical phenotype maturation of the enteric nervous system correlated to the evolution of the colonic motor response in newborn rats

P. de Vries, R. Soret, M. Neunlist, Y. Heloury

Brest, Nantes, France



Introduction: The digestive motor disorders of prematurity are related to he immaturity of the gastrointestinal tract. They delay feeding and expose them to infectious and surgical complications. The enteric nervous system (ENS), particularly the myenteric plexus, is a key component of the motor control of the gastrointestinal tract.

Aim: To characterize the evolution of neurochemical phenotype in particular cholinergic and nitrergic myenteric plexus of colon and to determine the functional impact of these changes on the neuro-motor induced response in the newborn rats during the first few days of life.

Material and Methods: The Sprague Dawley rats were sacrificed at day 1, 3, 5, 7, 14, 21 and 36. The colons have been harvest for immunohistochemical studies and functional ex vivo. After microdissection, the myenteric plexuses were labeled with fluorescent antibodies anti-acetylcholine transferase (ChAT), nitric-oxide synthase (NOS) and HuC / D (general neuronal marker). In an organ chamber a colonic segment was connected to an isometric force transducer. The contractile response induced by an electrical stimulation (EFS) was studied in absence and in presence of nitrergic (L-NAME) and cholinergic (Atropine) inhibitors.

Results: The immunohistochemical studies showed an increasing proportion of cholinergic neurons between day 1 (2,5%) and day 21 (11,3%) and an increasing proportion of nitrergic neurons between day 1 (14,2%) and day 5 (19,8%). The analysis of the colonic motility showed the appearance of spontaneous activity beginning from day 5 and rhythmic and reproducible contractions beginning with day 14 whose frequency increased significantly after day 21. On the other hand the response to EFS, visible from day 1, was atropine-sensitive beginning with day 5 and also L-NAME-sensitive beginning with day 21.

Conclusion: The postnatal modifications of the neurochemical phenotype of myenteric plexus are correlated with the changes in the colonic motor response. A better understanding of these phenomena would help for a better management of the digestive motor dysfunctions in premature children.


Key words: prematurity, enteric nervous system, immunohistochemical studies