RT Journal Article
SR Electronic
T1 Glucocorticoid Hormones Decrease Proliferation of Embryonic Neural Stem Cells through Ubiquitin-Mediated Degradation of Cyclin D1
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 5402
OP 5410
DO 10.1523/JNEUROSCI.4906-05.2006
VO 26
IS 20
A1 Maria Sundberg
A1 Suvi Savola
A1 Anni Hienola
A1 Laura Korhonen
A1 Dan Lindholm
YR 2006
UL http://www.jneurosci.org/content/26/20/5402.abstract
AB Corticosteroids can influence brain function, and glucocorticoid hormone receptors (GRs) are present in brain tissue. We observed that GR and also mineralocorticoid receptor (MR) are expressed by embryonic rat neural stem cells (NSCs). NSCs in developing ventricular epithelium were positive for GR. Stimulation of cultured NSCs with the specific receptor ligands dexamethasone and corticosterone reduced cell proliferation, shown by 5′-bromo-2-deoxy-uridine labeling. The effect of the hormones was dose dependent and inhibited by the GR blocker mifepristone but not by spironolactone, blocking MR. Dexamethasone inhibited the cell cycle by decreasing the levels of cyclin D1 in NSCs. The hormone-induced decline was inhibited by MG132 (benzyloxycarbonyl-leucyl-leucyl-leucinal), showing an involvement of the ubiquitin proteasome system, In keeping with this, dexamethasone increased the ubiquitination of cyclin D1. In embryonic brain, dexamethasone inhibited cell proliferation of NSCs. This demonstrates that embryonic NSCs are critically influenced by glucocorticoids, which can have long-term effects in the brain.