NGF but not GDNF or neurturin enhance acetylcholine tissue levels in striatal organotypic brain slices.

ABSTRACT

Trophic factors play important roles in survival and nerve fiber growth of cholinergic interneurons in the striatum in vivo and in vitro. In this study an organotypic slice model was used to investigate the effects of nerve growth factor and the novel factors glial cell line-derived neurotrophic factor and neurturin as well as other trophic factors on the striatal acetylcholine tissue levels During culturing over 2 weeks acetylcholine tissue levels markedly decreased, representing degeneration of cholinergic neurons. When striatal slices were cultured for 2 weeks in the presence of 100 ng/ml nerve growth factor tissue levels of acetylcholine and the expression of choline acetyltransferase-like immunoreactivity and mRNA, as well as the muscarinic M2 autoreceptor mRNA were markedly enhanced compared to slices cultured without or with 10 ng/ml nerve growth factor. A single administration of nerve growth factor had no effect on acetylcholine tissue levels suggesting that nerve growth factor does not directly increase acetylcholine synthesis. All other trophic factors (glial cell line-derived neurotrophic factor, neurturin, brain-derived neurotrophic factor, neurotrophin-3 and -4/5, fibroblast growth factor-2, insulin like growth factor-I) had no effects on acetylcholine tissue levels. Thus, the organotypic slice model is a suitable system to study the effects of trophic factors and it is concluded that nerve growth factor selectively enhances acetylcholine tissue levels, indicating protection of cholinergic interneurons in the dorsal striatum.