Dose-related effects of nerve growth factor (NGF) on choline acetyltransferase (ChAT), acetylcholine (ACh) content and ACh turnover in the brain of newborn rats

Abstract

Dose-effect relations of ?-nerve growth factor (NGF) have been established on the induction of choline acetyltransferase (ChAT) in basal forebrain nuclei, striatum, cortex and hippocampus of newborn rats after single intracerebroventricular (i.c.v.) injections. Doses above 2 ?g were maximally effective in each of the four brain regions. With the same doses and in the same time course acetylcholine (ACh) concentrations were elevated in the same brain regions. ChAT activity was increased up to 220% in the septum, 200% in the striatum, 160% in the cortex and 120% in the hippocampus. The ACh concentration was elevated up to 175% in the septum, 140% in the striatum, 130% in the cortex and 117% in the hippocampus. The incorporation of labelled choline into ACh showed an increase in ACh turnover of about 60% after i.c.v. application of 5 ?g NGF. Unspecific effects of NGF on brain growth have been excluded. NGF may possibly be useful for the treatment of memory and cognitive impairment as in senile dementia of Alzheimer's type.