Pharmacological restoration of gut barrier function in stressed neonates partially reverses long-term alterations associated with maternal separation.
Langue
EN
Article de revue
Ce document a été publié dans
Psychopharmacology. 2019-05, vol. 236, n° 5, p. 1583-1596
Résumé en anglais
Intestinal permeability plays an important role in gut-brain axis communication. Recent studies indicate that intestinal permeability increases in neonate pups during maternal separation (MS). The present study aims to ...Lire la suite >
Intestinal permeability plays an important role in gut-brain axis communication. Recent studies indicate that intestinal permeability increases in neonate pups during maternal separation (MS). The present study aims to determine whether pharmacological inhibition of myosin light chain kinase (MLCK), which regulates tight junction contraction and controls intestinal permeability, in stressed neonates, protects against the long-term effects of MS. Male Wistar rats were exposed to MS (3 h per day from post-natal day (PND)2 to PND14) or left undisturbed and received daily intraperitoneal injection of a MLCK inhibitor (ML-7, 5 mg/kg) or vehicle during the same period. At adulthood, emotional behaviors, corticosterone response to stress, and gut microbiota composition were analyzed. ML-7 restored gut barrier function in MS rats specifically during the neonatal period. Remarkably, ML-7 prevented MS-induced sexual reward-seeking impairment and reversed the alteration of corticosterone response to stress at adulthood. The effects of ML-7 were accompanied by the normalization of the abundance of members of Lachnospiraceae, Clostridiales, Desulfovibrio, Bacteroidales, Enterorhabdus, and Bifidobacterium in the feces of MS rats at adulthood. Altogether, our work suggests that improvement of intestinal barrier defects during development may alleviate some of the long-term effects of early-life stress and provides new insight on brain-gut axis communication in a context of stress.< Réduire
Mots clés en anglais
Animals
Animals
Newborn
Azepines
Corticosterone
Dose-Response Relationship
Drug
Female
Gastrointestinal Microbiome
Intestinal Mucosa
Male
Maternal Deprivation
Myosin-Light-Chain Kinase
Naphthalenes
Pregnancy
Rats
Rats
Wistar
Stress
Psychological
Time Factors
Unités de recherche