PMID- 34888841
OWN - NLM
STAT- MEDLINE
DCOM- 20211213
LR  - 20220531
IS  - 2190-5215 (Print)
VI  - 26
DP  - 2021
TI  - Ketamine Action on Astrocytes Provides New Insights into Rapid Antidepressant 
      Mechanisms.
PG  - 349-365
LID - 10.1007/978-3-030-77375-5_14 [doi]
AB  - Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, 
      exerts rapid, potent and long-lasting antidepressant effect already after a 
      single administration of a low dose into depressed individuals. Apart from 
      targeting neuronal NMDARs essential for synaptic transmission, ketamine also 
      interacts with astrocytes, the principal homoeostatic cells of the central 
      nervous system. The cellular mechanisms underlying astrocyte-based rapid 
      antidepressant effect are incompletely understood. Here we overview recent data 
      that describe ketamine-dependent changes in astrocyte cytosolic cAMP activity 
      ([cAMP](i)) and ketamine-induced modifications of stimulus-evoked Ca(2+) 
      signalling. The latter regulates exocytotic release of gliosignalling molecules 
      and stabilizes the vesicle fusion pore in a narrow configuration that obstructs 
      cargo discharge or vesicle membrane recycling. Ketamine also instigates rapid 
      redistribution of cholesterol in the astrocyte plasmalemma that may alter flux of 
      cholesterol to neurones, where it is required for changes in synaptic plasticity. 
      Finally, ketamine attenuates mobility of vesicles carrying the inward rectifying 
      potassium channel (K(ir)4.1) and reduces the surface density of K(ir)4.1 channels 
      that control extracellular K(+) concentration, which tunes the pattern of action 
      potential firing in neurones of lateral habenula as demonstrated in a rat model 
      of depression. Thus, diverse, but not mutually exclusive, mechanisms act 
      synergistically to evoke changes in synaptic plasticity leading to sustained 
      strengthening of excitatory synapses necessary for rapid antidepressant effect of 
      ketamine.
CI  - (c) 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.
FAU - Stenovec, Matjaz
AU  - Stenovec M
AD  - Celica BIOMEDICAL, Ljubljana, Slovenia.
AD  - Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of 
      Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, 
      Slovenia.
FAU - Li, Baoman
AU  - Li B
AD  - Practical Teaching Centre, School of Forensic Medicine, China Medical University, 
      Shenyang, China.
AD  - Department of Poison Analysis, School of Forensic Medicine, China Medical 
      University, Shenyang, China.
FAU - Verkhratsky, Alexei
AU  - Verkhratsky A
AD  - Celica BIOMEDICAL, Ljubljana, Slovenia.
AD  - Faculty of Biology, Medicine and Health, The University of Manchester, 
      Manchester, UK.
AD  - Achucarro Center for Neuroscience, IKERBASQUE, Bilbao, Spain.
FAU - Zorec, Robert
AU  - Zorec R
AD  - Celica BIOMEDICAL, Ljubljana, Slovenia. robert.zorec@mf.uni-lj.si.
AD  - Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of 
      Pathophysiology, Faculty of Medicine, University of Ljubljana, Ljubljana, 
      Slovenia. robert.zorec@mf.uni-lj.si.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Adv Neurobiol
JT  - Advances in neurobiology
JID - 101571545
RN  - 0 (Antidepressive Agents)
RN  - 690G0D6V8H (Ketamine)
SB  - IM
MH  - Animals
MH  - Antidepressive Agents
MH  - Astrocytes
MH  - Exocytosis
MH  - *Ketamine/pharmacology
MH  - Rats
MH  - Synapses
OTO - NOTNLM
OT  - Astrocytes
OT  - Cholesterol
OT  - Endocytosis
OT  - Excitability
OT  - Exocytosis
OT  - Ketamine
EDAT- 2021/12/11 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/12/10 06:59
PHST- 2021/12/10 06:59 [entrez]
PHST- 2021/12/11 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
AID - 10.1007/978-3-030-77375-5_14 [doi]
PST - ppublish
SO  - Adv Neurobiol. 2021;26:349-365. doi: 10.1007/978-3-030-77375-5_14.