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

ABSTRACT

Maternal separation in neonatal rodents causes a wide range of behavioural and metabolic alterations, affecting the physiological response of the neuro-immune-endocrine system. For example, interference with the normal mother-infant interactions leads to an increased susceptibility to experimentally-induced allergic encephalomyelitis (EAE) in adult life. Since it has been reported that mast cells (MCs) participate in the pathophysiology of the autoimmune inflammatory disease multiple sclerosis (MS) and also EAE and that brain nerve growth factor (NGF) levels are altered in EAE, studied whether maternal separation and gentle manipulation (gentling) of neonatal Lewis rats perturb NGF levels or MC distribution in the brain. EAE-induction susceptibility in adult life was also evaluated and NGF levels and mast cell distribution within the hippocampus and thalamus were measured at 0, 10, 20 and 60 postnatal days. Our results show an exacerbation of clinical signs in rats separated from mothers where EAE was induced, a general decrease in NGF protein levels and MC number in the hippocampus during the first developmental period and significant increase in the number of MC in the hippocampus and the thalamus at young-adulthood (60 days of age). These results indicate that disruption of the maternal bond during early infancy may produce long-lasting alterations in the brain cellular and molecular environment, leading to increased susceptibility to EAE in adult life.