Ketamine alters functional plasticity of astroglia

ǂan ǂimplication for antidepressant effect

Povzetek

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 (Kir4.1) to the plasmalemma that reduces the surface density of Kir4.1. 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.

Ključne besede

astrociti;ketamin;eksocitoza;astrocytes;ketamine;exocytosis;

Podatki

Jezik:	Angleški jezik
Leto izida:	2021
Tipologija:	1.02 - Pregledni znanstveni članek
Organizacija:	UL MF - Medicinska fakulteta
UDK:	616-092
COBISS:	67452931
ISSN:	2075-1729
Št. ogledov:	119
Št. prenosov:	41
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Slovenski jezik
Sekundarne ključne besede:	astrociti;ketamin;eksocitoza;
Vrsta dela (COBISS):	Članek v reviji
Strani:	str. 1-18
Letnik:	ǂVol. ǂ11
Zvezek:	ǂiss. ǂ6
Čas izdaje:	2021
DOI:	10.3390/life11060573
ID:	14889984