Neonatal stress affects vulnerability of cholinergic neurons and cognition in the rat: Involvement of the HPA axis

Adverse experiences early in life may sensitize specific neurocircuits to subsequent stressors. We have evaluated in maternal separation (MS) rats, an animal paradigm of early-life stress, the effects of a selective cholinergic lesion on cognitive function as well as susceptibility of cholinergic neurons to the lesion. MS rats subjected to a cholinergic lesion by administration of the immunotoxin 192 IgG-saporin, showed significant decreases in both choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity compared to control lesioned rats. Morris water maze results revealed a significant impairment in learning and memory function in MS adult rats and further cognitive deficits after the lesion. The lesion of cholinergic neurons induced a significant decrease in glucocorticoid receptor density in MS rats, accompanied by increases in CRF mRNA expression. Decreases in NGF and increases in NGF-p75NTR expression have also been found in MS rats. Our results suggest that vulnerability of basal forebrain cholinergic nerve cells might be affected by the HPA axis. The present data are discussed not only in terms of conditions that occur during ageing or Alzheimer disease, but also regarding a purported involvement of the cholinergic system in the regulation of HPA axis activity. (C) 2009 Elsevier Ltd. All rights reserved.