Does senile impairment of cholinergic system in rats concern only disturbances in cholinergic phenotype or the progressive degeneration of neuronal cell bodies?

The trophic effect of continuous intraventricular infusion of nerve growth factor (NGF) on morphology of the basal forebrain (BF) cholinergic neurons was tested in 4- and 28-month-old male Wistar rats. All studies were conduc ted using behaviorally uncharacterized animals fi om the same breeding colo ny. Immunohistochemical procedure for choline acetyltransferase (ChAT) and p75(NTR) receptor has been applied to identify cholinergic cells in the str uctures of basal forebrain (BF), Using a quantitative image analyzer, morph ometric and densitometric parameters of ChAT- and p75(NTR) -positive cells were measured immediately after cessation of NGF infusion. In 28-month-old non-treated rats the number of intensively ChAT-positive cells in all foreb rain structures was reduced by 50-70% as compared with young animals. The r emaining ChAT-positive cells appeared shrunken and the neuropil staining wa s markedly reduced. In contrast, the same neurons when stained for p75(NTR) were numerous and distinctly visible with perfect morphology. Analysis of Nissl stained sections also showed that 28-month-old rats did not display s ignificant losses of neuronal cell bodies. NGF restored the number of inten sely stained ChAT-positive cells to about 90% of that for young controls an d caused a significant increase in size of those cells in 28-month-old rats as compared with the control, age-matched group. NGF did not influence the morphology of p75(NTR)-positive neurons, which were well labeled, irrespec tive of treatment and age of the rats. In 4-month-oId rats, NGF infusion de creased the intensity of both ChAT and p75(NTR) immunostaining. These data provide some evidence for preservation of BF cholinergic neurons from atrop hy during aging and indicate that senile impairment of the cholinergic syst em in rats concerns decrease in ChAT-protein expression rather than an acut e degeneration of neuronal cell bodies. Treatment with NGF resulted in rest oration of cholinergic phenotype in the BF neurons of aged rats. However, t he present study also rises issue of possible detrimental effects of NGF in young normal animals.