Abbreviations used: ACh, acetylcholine; AM, acetoxymethyl ester; APV, DL(-)-2-amino-5-phosphonovaleric acid; BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid; BDNF, brain-derived neurotrophic factor; [Ca2+]i, intracellular Ca2+ concentration; CaMK, Ca2+/calmodulin-dependent protein kinase; cAMP, cyclic AMP; ChAT, choline acetyltransferase; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; CREB, cyclic AMP-response element-binding protein; MEK, mitogen-activated protein kinase kinase; NGF, nerve growth factor; NT, neurotrophin; NT-3, neurotrophin-3; NT-4, neurotrophin-4; PKA, protein kinase A.
Brief Exposure to Neurotrophins Produces a Calcium-Dependent Increase in Choline Acetyltransferase Activity in Cultured Rat Septal Neurons
Article first published online: 19 MAR 2003
Journal of Neurochemistry
Volume 74, Issue 3, pages 988–999, March 2000
How to Cite
Nonner, D., Barrett, E. F. and Barrett, J. N. (2000), Brief Exposure to Neurotrophins Produces a Calcium-Dependent Increase in Choline Acetyltransferase Activity in Cultured Rat Septal Neurons. Journal of Neurochemistry, 74: 988–999. doi: 10.1046/j.1471-4159.2000.0740988.x
- Issue published online: 19 MAR 2003
- Article first published online: 19 MAR 2003
- Nerve growth factor;
- Brain-derived neurotrophic factor;
- Choline acetyltransferase;
- Basal forebrain cholinergic neurons
Abstract: We demonstrate that brief (30-min) exposure of cultured embryonic rat septal neurons to neurotrophins (NTs) increases choline acetyltransferase (ChAT) activity by 20-50% for all tested NTs (nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4, each at 100 ng/ml). The increase in ChAT activity was first detected 12 h after NT exposure, persisted at least 48 h, and was not mediated by increased neuronal survival or action-potential activity. Under some conditions, the response to brief NT exposure was as great as that produced by continuous exposure. NT stimulation of ChAT activity was inhibited by inhibitors of p75- and Trk kinase-mediated signaling, by removal of extracellular Ca2+ during the period of NT exposure, and by buffering intracellular Ca2+ with BAPTA. Application of nerve growth factor and brain-derived neurotrophic factor transiently increased [Ca2+] within a subpopulation of neurons. NT stimulation of ChAT activity was not affected significantly by cyclic AMP agonists or antagonists. These findings suggest that brief exposure to NTs can have a long-lasting effect on cholinergic transmission, and that this effect requires Ca2+, but not cyclic AMP.