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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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