20.500.12556/RUL-128746 Astrocyte specific remodeling of plasmalemmal cholesterol composition by ketamine indicates a new mechanism of antidepressant action Ketamine is an antidepressant with rapid therapeutic onset and long-lasting effect, although the underlying mechanism(s) remain unknown. Using FRET-based nanosensors we found that ketamine increases [cAMP]$_i$ in astrocytes. Membrane capacitance recordings, however, reveal fundamentally distinct mechanisms of effects of ketamine and [cAMP]$_i$ on vesicular secretion: a rise in [cAMP]$_i$ facilitated, whereas ketamine inhibited exocytosis. By directly monitoring cholesterol-rich membrane domains with a fluorescently tagged cholesterol-specific membrane binding domain (D4) of toxin perfringolysin O, we demonstrated that ketamine induced cholesterol redistribution in the plasmalemma in astrocytes, but neither in fibroblasts nor in PC 12 cells. This novel mechanism posits that ketamine affects density and distribution of cholesterol in the astrocytic plasmalemma, consequently modulating a host of processes that may contribute to ketamine's rapid antidepressant action. astrocytes ketamine cholesterol astrociti ketamin holesterol true false true Angleški jezik Slovenski jezik Članek v reviji 2021-07-27 11:15:00 2021-07-27 11:15:02 2022-09-07 04:16:57 0000-00-00 00:00:00 2019 0 0 12 str. Vol. 9, art. 10957 July 2019 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-092 2045-2322 10.1038/s41598-019-47459-z 34434009 RAZ_Lasic_Eva_2019.pdf RAZ_Lasic_Eva_2019.pdf 1 3AF963E16CFB141AC7438CE03F6B0754 de7ce63f896eec8828f140f1f1e87d8bb0a314ce2a5b1a842ee062b4264a6c2a f5489d8b-eeba-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=145592 https://www.nature.com/articles/s41598-019-47459-z 0 205f349a-eebb-11eb-a523-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=145593 Medicinska fakulteta 0 0 0