Astrocyte specific remodeling of plasmalemmal cholesterol composition by ketamine indicates a new mechanism of antidepressant action

Lasič, Eva (avtor), Lisjak, Marjeta (avtor), Horvat, Anemari (avtor), Božić, Mićo (avtor), Šakanović, Aleksandra (avtor), Anderluh, Gregor (avtor), Verkhratsky, Alexei (avtor), Vardjan, Nina (avtor), Jorgačevski, Jernej (avtor), Stenovec, Matjaž (avtor), Zorec, Robert (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: astrocytes, ketamine, cholesterol
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2019
• Št. strani: 12 str.
• Številčenje: Vol. 9, art. 10957
• PID: 20.500.12556/RUL-128746
• UDK: 616-092
• ISSN pri članku: 2045-2322
• DOI: 10.1038/s41598-019-47459-z
• COBISS.SI-ID: 34434009
• Datum objave v RUL: 27.07.2021

Gradivo je del revije

• Naslov: Scientific reports
• Skrajšan naslov: Sci. rep.
• Založnik: Nature Publishing Group
• ISSN: 2045-2322
• COBISS.SI-ID: 18727432

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 29.07.2019

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: astrociti, ketamin, holesterol