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Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine

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Abstract

Objective

Here, we present the data indicating that chronic treatment with fluoxetine regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence.

Results

At lower concentrations, fluoxetine downregulates gene expression of Cav-1, decreases membrane content of PTEN, increases activity of PI3K/AKT, and elevates GSK-3β phosphorylation thus suppressing its activity. At higher concentrations, fluoxetine acts in an inverse fashion. As expected, fluoxetine at lower concentrations increased while at higher concentrations decreased glycogen content in astrocytes.

Conclusions

Our findings indicate that bi-phasic regulation of glycogen content via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine may be responsible for both therapeutic and side effects of the drug.

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Acknowledgements

This study was supported by Grant No. 31400925 to DS from the National Natural Science Foundation of China.

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Authors and Affiliations

  1. Laboratory of Metabolic Brain Diseases, Institute of Metabolic Disease Research and Drug Development, China Medical University, No. 77, Puhe Road, Shenbei District, Shenyang, People’s Republic of China

    Qiufang Bai, Dan Song, Li Gu & Liang Peng

  2. Faculty of Life Science, The University of Manchester, Manchester, UK

    Alexei Verkhratsky

  3. Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain

    Alexei Verkhratsky

Authors
  1. Qiufang Bai
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  2. Dan Song
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  3. Li Gu
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  4. Alexei Verkhratsky
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  5. Liang Peng
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Correspondence to Liang Peng.

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The authors declare that they have no conflict of interest.

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QB and DS contributed equally to this article.

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Bai, Q., Song, D., Gu, L. et al. Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine. Psychopharmacology 234, 1069–1077 (2017). https://doi.org/10.1007/s00213-017-4547-3

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  • DOI: https://doi.org/10.1007/s00213-017-4547-3

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