Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay

• Published in: The Journal of physiology 2007-04, Vol.580 (1), p.347-356
• Main Authors: Barreau, Frederick, Cartier, Christel, Leveque, Mathilde, Ferrier, Laurent, Moriez, Raphael, Laroute, Valerie, Rosztoczy, Andras, Fioramonti, Jean, Bueno, Lionel
• Format: Article
• Language: English
• Subjects: Animals; Colon - physiology; Corticotropin-Releasing Hormone - pharmacology; Corticotropin-Releasing Hormone - physiology; Female; Hormone Antagonists - pharmacology; Immunohistochemistry; Integrative; Intestinal Mucosa - drug effects; Intestinal Mucosa - physiology; Life Sciences; Male; Mast Cells - drug effects; Mast Cells - metabolism; Mast Cells - physiology; Maternal Deprivation; Mifepristone - pharmacology; Nerve Growth Factor - metabolism; Nerve Growth Factor - physiology; Peptide Fragments - pharmacology; Permeability; Pregnancy; Rats; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone - drug effects; Receptors, Corticotropin-Releasing Hormone - metabolism; Thiazoles - pharmacology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2006.120907

Neonatal maternal deprivation (NMD) increases gut paracellular permeability (GPP) through mast cells and nerve growth factor (NGF), and modifies corticotrophin-releasing factor (CRF) and corticosterone levels. CRF, corticosterone and mast cells are involved in stress-induced mucosal barrier impairment. Consequently, this study aimed to specify whether corticosteronaemia and colonic expression of both preproCRF and CRF are modified by NMD, and to determine if altered expression may participate in the elevated GPP in connection with NGF and mast cells. Male Wistar rat pups were either separated from postnatal days 2–14, or left undisturbed with their dam. At 12 weeks of age, adult rats were treated with mifepristone (an antagonist of corticoid receptors), α-helical CRF (9-41) (a non-specific CRF receptor antagonist), or SSR-125543 (CRF-R 1 receptor antagonist). We also determined corticosteronaemia and both colonic preproCRF and CRF expression. Then, control rats were treated by CRF, doxantrazole (mast cell stabilizer), BRX-537A (a mast cell activator) and anti-NGF antibody. NMD did not modify colonic CRF level but increased colonic preproCRF expression and corticosteronaemia. Peripheral CRF, via CRF-R 1 receptor, but not corticosterone, was involved in the elevated GPP observed in these rats, through a mast-cell-mediated mechanism, since the increase of GPP induced by exogenous CRF was abolished by doxantrazole. Anti-NGF antibody treatment also reduced the elevated GPP induced by CRF or BRX-537A. CRF acts through CRF-R 1 receptors to stimulate NGF release from mast cells, which participates in the elevated GPP observed in NMD adult rats. This suggests that early traumatic experience induced neuro-endocrine dysfunction, involved in alterations of gut mucosal barrier.