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Int J Neuropsychopharmacol. 2014 Dec 7;18(5). pii: pyu099. doi: 10.1093/ijnp/pyu099.

Fluoxetine regulates neurogenesis in vitro through modulation of GSK-3β/β-catenin signaling.

Author information

1
Department of Critical Care Medicine, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China (Drs Hui and Yan); Department of Neurology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China (Drs J Zhang, Li, Mao, Shi, and Xi); Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA (Drs Kim, Tong, and Ying); Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China (Dr Z Zhang).
2
Department of Critical Care Medicine, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China (Drs Hui and Yan); Department of Neurology, Wuxi People's Hospital of Nanjing Medical University, Wuxi, China (Drs J Zhang, Li, Mao, Shi, and Xi); Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Cell and Neurobiology, University of Southern California, Los Angeles, CA (Drs Kim, Tong, and Ying); Department of Neurology, Affiliated ZhongDa Hospital of Southeast University, Nanjing, China (Dr Z Zhang). xiguangjun@163.com.

Abstract

BACKGROUND:

It is generally accepted that chronic treatment with antidepressants increases hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling was shown to be involved in the mechanism of how antidepressants might influence hippocampal neurogenesis.

METHODS:

The aim of this study was to determine whether GSK-3β/β-catenin signaling is involved in the alteration of neurogenesis as a result of treatment with fluoxetine, a selective serotonin reuptake inhibitor. The mechanisms involved in fluoxetine's regulation of GSK-3β/β-catenin signaling pathway were also examined.

RESULTS:

Our results demonstrated that fluoxetine increased the proliferation of embryonic neural precursor cells (NPCs) by up-regulating the phosphorylation of Ser9 on GSK-3β and increasing the level of nuclear β-catenin. The overexpression of a stabilized β-catenin protein (ΔN89 β-catenin) significantly increased NPC proliferation, while inhibition of β-catenin expression in NPCs led to a significant decrease in the proliferation and reduced the proliferative effects induced by fluoxetine. The effects of fluoxetine-induced up-regulation of both phosphorylation of Ser9 on GSK-3β and nuclear β-catenin were significantly prevented by the 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635.

CONCLUSIONS:

The results demonstrate that fluoxetine may increase neurogenesis via the GSK-3β/β-catenin signaling pathway that links postsynaptic 5-HT1A receptor activation.

KEYWORDS:

cell proliferation; fluoxetine; glycogen synthase kinase-3 beta; neural precursor cells; β-catenin

PMID:
25522429
PMCID:
PMC4376550
DOI:
10.1093/ijnp/pyu099
[Indexed for MEDLINE]
Free PMC Article

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