Prior neonatal isolation reduces induction of NGF mRNA and decreases GDNF mRNA in the hippocampus of juvenile and adult rodents subjected to immobilization stress

Abstract

Numerous studies have demonstrated that early adverse experiences are associated with the development of susceptibility to stress later in life. Although it is known that early experience of adversity, such as neonatal isolation, maternal separation, and low maternal care, enhances the activity of the hypothalamo-pituitary-adrenalaxis in rodents, the detailed mechanism underlying stress susceptibility induced by early adversity remains to be elucidated. Since neurotrophins have been shown to have a neuroprotective effect, we examined the influence of repeated neonatal isolation on expression of nerve growth factor (NGF), glia cell-derived neurotrophic factor (GDNF), and neurotrophin-3 mRNA in the hippocampus of juvenile and adult rats subsequently exposed immobilization stress, using real-time quantitative PCR and in situ hybridization. Neonatal isolation did not affect the basal hippocampal expression of these neurotrophin mRNAs in either juvenile or adult rats not subsequently exposed to immobilization. Similarly, there was a significant interaction between neonatal isolation and immobilization that affected the expression of NGF and GDNF mRNAs. Neonatal isolation attenuated the induction of NGF mRNA in both groups of rats and decreased GDNF mRNA in juvenile rats in response to immobilization. The decreased induction of NGF mRNA and reduced GDNF mRNA in response to immobilization was found in the CA3 pyramidal cell layer and dentate gyrus granular cell layer in the hippocampus of adult rats that had been subjected to neonatal isolation. These findings suggest that susceptibility to stress arising from prior neonatal isolation might be a result of decreased neuroprotective support through NGF and GDNF.