Background: Neonatal maternal deprivation induces colonic alterations in adult rats, such as hypersensitivity to distension or increase in paracellular permeability, characterizing IBS patients. Recent studies described neuro-immune alterations in the colonic mucosa of IBS patients.
Methods: Male Wistar were submitted to maternal deprivation 3 h daily during postnatal days 2-14, and were sacrificed at 4 or 12 weeks of age. Control pups were left undisturbed with their dam.
Results: Colonic mast cell hyperplasia was observed at 4 and 12 weeks in maternally deprived rats, and was associated with an increase in protease content. Mucosal nerve fibre density assessed by PGP 9.5 immunoreactivity was increased at 12 but not 4 weeks, while CGRP-immunoreactive fibres remain constant. Synaptogenesis assessed by synaptophysin immunostaining was increased at 4 but not 12 weeks. The number of mast cells in close proximity with PGP 9.5 or CGRP-IR fibres was greater at both 4 and 12 weeks. Expression of neurokinin NK1 receptors in the spinal cord was enhanced at 12 weeks. No significant change in total mast cell number, PGP 9.5 immunoreactivity and mast cells associated with PGP 9.5-IR fibres was observed in the jejunum. Treatment of pups with anti-NGF antibodies abolished the increases in synaptogenesis and in the number of mast in cells close proximity with nerve fibres observed 4 weeks after maternal deprivation.
Conclusions: Neonatal maternal deprivation induces closer association of colonic mast cells to nerves, which is similar to that seen in irritable bowel syndrome (IBS) patients. Nerve growth factor (NGF) is a possible mediator of this effect.
- Colonic mucosa
- Enteric nerves
- Irritable bowel syndrome
- Mast cells
- Neonatal stress