Environmental manipulation early in life can alter the development of the hypothalamic-pituitary-adrenal (HPA) axis by mechanisms that are still unclear. The aim of the present work was to study the acute effects of postnatal touch stimulation, in an attempt to understand the mechanism by which touch stimulation early in life alters the HPA response to stress in adult animals. Rat pups were gently brushed for 15 min daily during the 1st postnatal week. Serum corticosterone levels were determined by radioimmunoassays, while glucocorticoid receptor (GR) gene expression was assayed by semiquantitative reverse transcriptase-polymerase chain reaction. Touch stimulation induced a significant decrease (30–36%) in serum corticosteroid secretion during the 1st and 2nd postnatal day as compared to the unstimulated group. In contrast, GR gene expression in the touch stimulation group was significantly increased in several brain areas such as the hippocampus (19–21%), frontal cortex (26–34%) and midbrain (15–24%). The results thus indicate that neonatal touch stimulation causes acute hormone- secretion and gene-expression changes within the period of stimulation. These changes may be the underlying cause for the permanent changes that have been observed in adult animals touch-stimulated as neonates.
In the offspring of prenatal stress animals, overactivity and impaired negative feedback regulation of the hypothalamic-pituitary-adrenal axis are consistent finding. However, little was known about how prenatal stress can permanently alter developmental trajectories of pup's brain. Growth-associated protein-43 (GAP-43) is a presynaptic membrane phosphoprotein whose expression increases during developmental events such as axonal outgrowth or remodeling and synaptogenesis. Phosphorylation of GAP-43 by protein kinase C was correlated with enhanced axonal growth and transmitter release. In adult animals, increase of GAP-43 correlated with monoaminergic deficit in neuropsychiatric disorders. The present study examines the effects of repeated maternal restraint stress on the level of GAP-43 in the brain of rat pups. The results showed that prenatal stress significantly increased GAP-43 level in the PFC of rat pup during PND 7-14 as compared to control but not significant difference when observed at PND 21. Increased GAP-43 expression was also observed in the pup's hippocampus during the same postnatal periods. However, when observed at PND 60, pups born from stressed mother showed a significant lower (p<0.001) GAP-43 expression as compare with control group. These changes indicate the direct effect of corticosteroid hormone, since repeated maternal injection with corticosterone (CORT, 40 mg/kg) during GD 14-21 also gave the same results. PND 7-14 is the peak period of synaptogenesis in these brain areas and abnormal axon sprouting and reorganization may lead to a defect in synaptic pruning at later stage of life. The results suggested that maternal stress is harmful to the developing brain and upregulation of GAP-43 indicated a protective mechanism against the toxicity of maternal stress hormone. Prenatal stress alter the normal developmental trajectories in the pup's brain may underlies the mechanism link between early life stress and neuropsychopathology in later life.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.