Nerve growth factor selectively increases cholinergic markers but not neuropeptides in rat basal forebrain in culture

Abstract

We have previously used organotypic cultures to study mechanisms regulating phenotypic expression of neurotransmitter characters in the brain. Our previous work indicated that nerve growth factor (NGF) specifically increased the activity of choline acetyltransferase (CAT) in striatal cholinergic interneurons. In the present study we examined the effect of NGF on neurons of fetal rat basal forebrain-medial septal area (BF-MS) maintained in organotypic culture. Treatment with 200 biological units/ml of NGF resulted in a 3- to 6-fold increase in the specific activity of CAT. This effect was specifically blocked by anti-NGF antiserum, whereas treatment with antiserum alone did not alter the cholinergic enzyme. NGF also elicited a marked increase in CAT staining intensity, using a monoclonal antibody directed against the enzyme. Further, the number of CAT-positive neurons appeared to increase in the NGF-treated cultures. Exposure to NGF also increased the activity of another cholinergic marker, the catabolic enzyme, acetylcholinesterase. The effect of NGF appeared to be highly selective, since substance P and somatostatin levels were unchanged by NGF treatment.