| First Author | Lau T | Year | 2013 |
| Journal | Neurosci Lett | Volume | 554 |
| Pages | 115-20 | PubMed ID | 24021805 |
| Mgi Jnum | J:207873 | Mgi Id | MGI:5559837 |
| Doi | 10.1016/j.neulet.2013.08.070 | Citation | Lau T, et al. (2013) Nongenomic, glucocorticoid receptor-mediated regulation of serotonin transporter cell surface expression in embryonic stem cell derived serotonergic neurons. Neurosci Lett 554:115-20 |
| abstractText | Depressive disorders have been linked to the combined dysregulation of the hypothalamus-pituitary-adrenal (HPA)-axis and the serotonergic system. The HPA-axis and serotonergic (5-HT) neurons exert reciprocal regulatory actions. It has been reported that glucocorticoid-glucocorticoid receptor (GR) signaling influences serotonin transporter (5-HTT) transcription but data also points to the fact that 5-HTT expression is regulated nongenomically via redistribution of 5-HTT from the cell surface into intracellular compartments. In order to analyze the acute effects of glucocorticoids on 5-HTT cell surface localization we differentiated serotonergic neurons from mouse embryonic stem (ES) cells derived from the C57BL/6N blastocysts. These postmitotic 5-HT neurons express all relevant serotonergic markers following the application of a growth factor-based differentiation protocol. Increasing concentrations of the GR agonist dexamethasone (Dex) resulted in enhanced, dose-dependent 5-HTT cell surface localization in the presence of the protein synthesis inhibitor cycloheximide already 1h after incubation. Inhibition of GR function by the specific GR-antagonist mifepristone abolished the increase in 5-HTT cell surface localization. Hence, our data account for a nongenomic upregulation of 5-HTT cell surface expression by glucocorticoid-GR interaction which likely constitutes a rapid physiological response to increased levels of glucocorticoids as seen during stress. Taken together, we provide a cellular model to analyze and dissect glucocorticoid-5HTT interactions on a molecular level that corresponds to in vivo animal models using C57BL/6N mice. |
