Fluoxetine attenuates the inhibitory effect of glucocorticoid hormones on neurogenesis in vitro via a two-pore domain potassium channel, TREK-1.
BACKGROUND
Sustained stress and elevated glucocorticoid reduces neurogenesis, whereas chronic treatment with antidepressants increases neurogenesis and blocks the effects of stress. Recently, TREK-1, a two-pore domain (K(2)p) potassium channel, has been shown to be involved in the mechanisms of major depression.


OBJECTIVE
This study aimed to investigate whether TREK-1 is involved in the alteration of neurogenesis according to glucocorticoids and antidepressants.


RESULTS
The present study addressed the expression of TREK-1 in neural stem cells (NSCs) and found TREK-1 was only associated with NSC proliferation. Bupivacaine and curcumin, two strong TREK-1 channel inhibitors, significantly increased embryonic NSC viability and proliferation while transfection of hTREK-1 decreased cell proliferation in embryonic NSCs. Dexamethasone, a glucocorticoid hormone receptor agonist, upregulated both protein and mRNA levels of TREK-1 leading to decreased NSC proliferation which could be reversed by bupivacaine. Fluoxetine, a serotonin reuptake inhibitor antidepressant that has been previously found to inhibit TREK-1 channels, robustly, could attenuate the upregulation of TREK-1 expression and the inhibition of NSC proliferation induced by dexamethasone.


CONCLUSIONS
Taken together, these data suggest that TREK-1 is associated with NSC proliferation and probably is a modulator of the effect that fluoxetine attenuates the inhibitory neurogenesis induced by glucocorticoid hormones.
The Department of Neurology, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, China.
Guangjun
G
Xi
Xiangrong
X
Zhang
Ling
L
Zhang
Yuxiu
Y
Sui
Jiaojie
J
Hui
Shanshan
S
Liu
Yingxin
Y
Wang
Lingjiang
L
Li
Zhijun
Z
Zhang
D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004347:Drug Interactions; D004622:Embryo, Mammalian; D005473:Fluoxetine / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007381:Intermediate Filament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D009433:Neural Inhibition / Q000187:drug effects*; D058953:Neural Stem Cells / Q000187:drug effects*; D055495:Neurogenesis / Q000187:drug effects*; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014162:Transfection / Q000379:methods
D001973:Bromodeoxyuridine; D005473:Fluoxetine; D005938:Glucocorticoids; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; D064231:Nestin; D024683:Potassium Channels, Tandem Pore Domain; D017367:Selective Serotonin Reuptake Inhibitors; C577484:NES protein, human; C577486:Nes protein, rat; C103742:potassium channel protein TREK-1