期刊
PSYCHOPHARMACOLOGY
卷 214, 期 3, 页码 747-759出版社
SPRINGER
DOI: 10.1007/s00213-010-2077-3
关键词
Neural stem cells; Glucocorticoids; Fluoxetine; Cell proliferation; Two-pore domain potassium channel; TREK-1
资金
- National Natural Science Foundation of China [30770779, 30825014, 30830046]
- National Basic Research Program of China (973 program) [2007CB512308, 2009CB918303]
- National Hi-Tech Research and Development Program of China (863 program) [2008AA02Z413]
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. This study aimed to investigate whether TREK-1 is involved in the alteration of neurogenesis according to glucocorticoids and antidepressants. 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. 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.
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