DECREASED CHOLINE-ACETYLTRANSFERASE ACTIVITY IN NERVE GROWTH FACTOR-TRANSGENIC MICE DURING BRAIN-DEVELOPMENT

Activity of the synthetic enzyme for acetylcholine, choline acetyltran sferase was investigated during development and in adult nerve growth factor-transgenic mice. A conspicuous reduction of choline acetyltrans ferase activity was observed in the anterior brain of nerve growth fac tor-transgenic embryos from embryonic days 13 to 16 (E13 to E16). Chol ine acetyltransferase activity levels subsequently resumed to normal l evels, with the exception of a 15% increase in the adult hippocampus. Nerve growth factor contents followed a similar time-course and region al distribution in normal and nerve growth factor-transgenic animals a nd displayed significantly higher values from E14 to the early postnat al period. Nerve growth factor contents were normal in the adult brain . In vitro experiments confirmed the involvement of nerve growth facto r in the decrease of choline acetyltransferase activity levels observe d in transgenic neurons during development. These results suggest a ro le for nerve growth factor in the initial phase of the phenotypic diff erentiation of cholinergic neurons. They show that nerve growth factor may, under specific developmental conditions, lead to a paradoxical d own-regulation of choline acetyltransferase activity.