Journal of Molecular Neuroscience

, Volume 49, Issue 2, pp 244–249 | Cite as

Fluoxetine Upregulates Phosphorylated-AKT and Phosphorylated-ERK1/2 Proteins in Neural Stem Cells: Evidence for a Crosstalk between AKT and ERK1/2 Pathways

  • Wen Huang
  • Yu Zhao
  • Xiaofeng Zhu
  • Zhiyou Cai
  • Shijun Wang
  • Shengtao Yao
  • Zhiguo Qi
  • Peng XieEmail author


Fluoxetine is a widely used antidepressant drug which inhibits the reuptake of serotonin in the central nervous system (CNS). Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the neuroprotection of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 50 μM fluoxetine significantly upregulated expression of the phosphorylated-AKT and ERK1/2 proteins in NSCs derived from rats. Besides, expression of phosphorylated-AKT and phosphorylated-ERK1/2 in fluoxetine-treated NSCs was effectively blocked (P < 0.05) by both PI3-K inhibitor (LY294002) and MEK inhibitor (PD98059). It was, therefore, concluded that the crosstalk between PI3K/AKT and MAPK/ERK pathways involved AKT and ERK1/2 phosphorylation by fluoxetine treatment. This study points to a novel role of fluoxetine in neuroprotection as an antidepressant drug and also unravels the crosstalk mechanism between the two signaling pathways.


Fluoxetine Neural stem cells Crosstalk 



Neural stem cells


Central nervous system


Institutional Animal Care and Use Committee


Hanks’ balanced salt solution


Dulbecco’s modified Eagle’s medium


Epidermal growth factor


Dimethyl sulfoxide


Sodium dodecyl sulfate


Polyacrylamide gel electrophoresis


Tris-Buffered Saline Tween-20


Analysis of variance


Ventral tegmental area



We thank the laboratory support staff for their help in this study. This work was supported by research grants from the National Natural Science Foundation of China (Grant # 81171113), the Natural Science Foundation of Chongqing, China (Grant # CSTC 2010BB5185, 2011BA5012), and the National Basic Research Program of China (973 Program, Grant # 2009CB918300).


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Wen Huang
    • 1
    • 2
  • Yu Zhao
    • 2
  • Xiaofeng Zhu
    • 3
  • Zhiyou Cai
    • 2
  • Shijun Wang
    • 4
  • Shengtao Yao
    • 5
  • Zhiguo Qi
    • 2
  • Peng Xie
    • 2
    Email author
  1. 1.Department of Neurology, Xinqiao HospitalThird Military Medical UniversityChongqingChina
  2. 2.Department of Neurology, the First Affiliated Hospital, Institute of NeuroscienceChongqing Medical UniversityChongqingChina
  3. 3.Institute of NeuroscienceJiamushi UniversityHeilongjiangChina
  4. 4.Department of Otorhinolaryngology, the First Affiliated HospitalJiamushi UniversityHeilongjiangChina
  5. 5.Department of neurosurgery, the First Affiliated HospitalChongqing Medical UniversityChongqingChina

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