Differential Regulation of Nerve Growth Factor (NGF) Synthesis in Neurons and Astrocytes by Glucocorticoid Hormones.
Glucocorticoid hormones are important regulators of brain development and ageing. Here we show that dexamethasone, a synthetic glucocorticoid, differentially affects the expression of nerve growth factor (NGF) in cultured neurons and astrocytes. Dexamethasone increased the levels of NGF mRNA in cultured hippocampal neurons in a time- and concentration-dependent manner, whereas it down-regulated the NGF mRNA levels in astrocytes. However, dexamethasone had no effect on the mRNA levels of brain-derived neurotrophic factor in the hippocampal neurons. Aldosterone, a mineralocorticoid, in higher concentrations also up-regulated NGF mRNA levels in the hippocampal neurons. Dexamethasone increased the levels of NGF mRNA in the rat hippocampus in vivo, but not to the same extent as observed with kainic acid, a glutamate receptor agonist. There is no apparent diurnal rhythm in the hippocampal NGF protein levels corresponding to circadian variations in the levels of glucocorticoid hormones in serum. The increase in NGF mRNA in the hippocampus in vivo following dexamethasone treatments may reflect the physiological response of hippocampal neurons to high glucocorticoid levels reached under conditions of stress.
Lindholm
Dan
D
Max Planck Institute for Psychiatry, Department of Neurochemistry, Am Klopferspitz 18A, D-8033 Martinsried bei München, FRG.
Castrén
Eero
E
Hengerer
Bastian
B
Zafra
Francisco
F
Berninger
Benedikt
B
Thoenen
Hans
H