Ketamine alters functional plasticity of astroglia : an implication for antidepressant effect

Stenovec, Matjaž (avtor)

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

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