Chronic glucocorticoid receptor activation impairs CREB transcriptional activity in clonal neurons.
Excessive circulating levels of glucocorticoids are thought to be associated with cognitive impairment. We provide evidence that chronic activation of the glucocorticoid receptor (GR) in clonal neurons inhibits the transcriptional activity of the cyclic AMP response element-binding protein (CREB), which is believed to be involved in memory processes. To investigate the underlying mechanism we studied the phosphorylation of CREB and found altered phosphorylation kinetics in neurons chronically treated with glucocorticoids. Our results demonstrate a hitherto unrecognized crosstalk between the cyclic AMP and glucocorticoid pathway and may provide the molecular basis for the effects of long-term glucocorticoid exposure on cognitive function.
Max-Planck-Institute for Neurological Research, European Graduate School for Neuroscience, Gleueler Strasse 50, D-50931 Cologne, Germany.
Melanie
M
Föcking
Irmgard
I
Hölker
Thorsten
T
Trapp
D000818:Animals; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D005576:Colforsin; D003907:Dexamethasone