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Ketamine alters functional plasticity of astroglia : an implication for antidepressant effect
ID
Stenovec, Matjaž
(
Avtor
)
PDF - Predstavitvena datoteka,
prenos
(1,19 MB)
MD5: 1F9C6C416A6E68EF49DD3A669FED3D2D
URL - Izvorni URL, za dostop obiščite
https://www.mdpi.com/2075-1729/11/6/573
Galerija slik
Izvleček
Ketamine, a non-competitive N–methyl–D–aspartate receptor (NMDAR) antagonist, exerts a rapid, potent and long-lasting antidepressant effect, although the cellular and molecular mechanisms of this action are yet to be clarified. In addition to targeting neuronal NMDARs fundamental for synaptic transmission, ketamine also affects the function of astrocytes, the key homeostatic cells of the central nervous system that contribute to pathophysiology of major depressive disorder. Here, I review studies revealing that (sub)anesthetic doses of ketamine elevate intracellular cAMP concentration ([cAMP]$_i$) in astrocytes, attenuate stimulus-evoked astrocyte calcium signaling, which regulates exocytotic secretion of gliosignaling molecules, and stabilize the vesicle fusion pore in a narrow configuration, possibly hindering cargo discharge or vesicle recycling. Next, I discuss how ketamine affects astrocyte capacity to control extracellular K$^+$ by reducing vesicular delivery of the inward rectifying potassium channel (K$_{ir}$4.1) to the plasmalemma that reduces the surface density of K$_{ir}$4.1. Modified astroglial K$^+$ buffering impacts upon neuronal firing pattern as demonstrated in lateral habenula in a rat model of depression. Finally, I highlight the discovery that ketamine rapidly redistributes cholesterol in the astrocyte plasmalemma, which may alter the flux of cholesterol to neurons. This structural modification may further modulate a host of processes that synergistically contribute to ketamine’s rapid antidepressant action.
Jezik:
Angleški jezik
Ključne besede:
astrocytes
,
ketamine
,
exocytosis
,
cAMP
,
endocytosis
,
fusion pore
,
K$_{ir}$4.1
,
vesicle mobility
,
cholesterol
Vrsta gradiva:
Članek v reviji
Tipologija:
1.02 - Pregledni znanstveni članek
Organizacija:
MF - Medicinska fakulteta
Status publikacije:
Objavljeno
Različica publikacije:
Objavljena publikacija
Leto izida:
2021
Št. strani:
17 str.
Številčenje:
Vol. 11, iss. 6, art. 573
PID:
20.500.12556/RUL-135741
UDK:
616-092
ISSN pri članku:
2075-1729
DOI:
10.3390/life11060573
COBISS.SI-ID:
67452931
Datum objave v RUL:
30.03.2022
Število ogledov:
753
Število prenosov:
124
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Objavi na:
Gradivo je del revije
Naslov:
Life
Skrajšan naslov:
Life
Založnik:
MDPI
ISSN:
2075-1729
COBISS.SI-ID:
519982617
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:
17.06.2021
Sekundarni jezik
Jezik:
Slovenski jezik
Ključne besede:
astrociti
,
ketamin
,
eksocitoza
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