DIFFERENTIAL-EFFECTS OF NERVE GROWTH-FACTOR ON EXPRESSION OF CHOLINE-ACETYLTRANSFERASE AND SODIUM-COUPLED CHOLINE TRANSPORT IN BASAL FOREBRAIN CHOLINERGIC NEURONS IN CULTURE

Nerve growth factor (NGF) treatment of primary cultures of embryonic d ay 17 rat basal forebrain differentially altered activity of choline a cetyltransferase (ChAT) and high-affinity choline transport; ChAT spec ific activity was increased by threefold in neurons grown in the prese nce of NGF for between 4 and 8 days, whereas high-affinity choline tra nsport activity was not changed relative to control. Dose-response stu dies revealed that enhancement of neuronal ChAT activity occurred at l ow concentrations of NGF with an EC(50) of 7 ng/ml, with no enhancemen t of high-affinity choline transport observed at NGF concentrations up to 100 ng/ml. In addition, synthesis of acetylcholine (ACh) and ACh c ontent in neurons grown in the presence of NGF for up to 6 days was in creased significantly compared with controls. These results suggest th at regulation of ACh synthesis in primary cultures of basal forebrain neurons is not limited by provision of choline by the high-affinity ch oline transport system and that increased ChAT activity in the presenc e of NGF without a concomitant increase in high-affinity choline trans port is sufficient to increase ACh synthesis. This further suggests th at intracellular pools of choline, which do not normally serve as subs trate for ACh synthesis, may be made available for ACh synthesis in th e presence of NGF.