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Astrocyte specific remodeling of plasmalemmal cholesterol composition by ketamine indicates a new mechanism of antidepressant action
ID
Lasič, Eva
(
Author
),
ID
Lisjak, Marjeta
(
Author
),
ID
Horvat, Anemari
(
Author
),
ID
Božić, Mićo
(
Author
),
ID
Šakanović, Aleksandra
(
Author
),
ID
Anderluh, Gregor
(
Author
),
ID
Verkhratsky, Alexei
(
Author
),
ID
Vardjan, Nina
(
Author
),
ID
Jorgačevski, Jernej
(
Author
),
ID
Stenovec, Matjaž
(
Author
),
ID
Zorec, Robert
(
Author
)
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https://www.nature.com/articles/s41598-019-47459-z
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Abstract
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.
Language:
English
Keywords:
astrocytes
,
ketamine
,
cholesterol
Work type:
Article
Typology:
1.01 - Original Scientific Article
Organization:
MF - Faculty of Medicine
Publication status:
Published
Publication version:
Version of Record
Year:
2019
Number of pages:
12 str.
Numbering:
Vol. 9, art. 10957
PID:
20.500.12556/RUL-128746
UDC:
616-092
ISSN on article:
2045-2322
DOI:
10.1038/s41598-019-47459-z
COBISS.SI-ID:
34434009
Publication date in RUL:
27.07.2021
Views:
977
Downloads:
168
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Record is a part of a journal
Title:
Scientific reports
Shortened title:
Sci. rep.
Publisher:
Nature Publishing Group
ISSN:
2045-2322
COBISS.SI-ID:
18727432
Licences
License:
CC BY 4.0, Creative Commons Attribution 4.0 International
Link:
http://creativecommons.org/licenses/by/4.0/
Description:
This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
Licensing start date:
29.07.2019
Secondary language
Language:
Slovenian
Keywords:
astrociti
,
ketamin
,
holesterol
Projects
Funder:
ARRS - Slovenian Research Agency
Project number:
P3-0310
Name:
Celična fiziologija
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-6790
Name:
Dinamične meritve metabolitov in sekundarnih prenašalcev v posameznem astrocitu v celični kulturi
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-6789
Name:
Patogeni mehanizem podaljšanih heksanukleotidnih ponovitev v genu C9orf72 pri nevrodegeneraciji
Funder:
ARRS - Slovenian Research Agency
Project number:
J3-7605
Name:
Nanofiziologija eksocitoze v zdravih in bolezenskih razmerah
Funder:
Other - Other funder or multiple funders
Funding programme:
CipKeBip
Funder:
Other - Other funder or multiple funders
Funding programme:
COST
Project number:
BM1002
Funder:
Other - Other funder or multiple funders
Funding programme:
COST
Project number:
CM1207
Acronym:
GLISTEN
Funder:
Other - Other funder or multiple funders
Funding programme:
COST
Acronym:
EuroCellNet
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