Neonatal handling in EAE-susceptible rats alters NGF levels and mast cell distribution in the brain

Maternal separation in neonatal rodents causes a wide range of behaviouralandmetabolic alterations, affecting the physiological response of theneuro-immune-endocrinesystem. For example, interference with the normal mother-infantinteractions leads to anincreased susceptibility to experimentally-induced allergicencephalomyelitis (EAE) in adult life.Since it has been reported that mast cells (MCs) participatein the pathophysiology of theautoimmune inflammatory disease multiple sclerosis (MS) and alsoEAE and that brain nervegrowth factor (NGF) levels are altered in EAE, we studied whethermaternal separation andgentle manipulation (gentling) of neonatal Lewis rats perturb NGF levelsor MC distribution inthe brain. EAE-induction susceptibility in adult life was also evaluated andNGF levels and mastcell distribution within the hippocampus and thalamus were measured at 0,10, 20 and 60postnatal days. Our results show an exacerbation of clinical signs in rats separatedfrom motherswhere EAE was induced, a general decrease in NGF protein levels and MC numberin thehippocampus during the first developmental period and a significant increase in the numberofMC in the hippocampus and the thalamus at young-adulthood (60 days of age). Theseresultsindicate that disruption of the maternal bond during early infancy may producelong-lastingalterations in the brain cellular and molecular environment, leading to increasedsusceptibility toEAE in adult life.