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Neurochemical Research

, Volume 43, Issue 8, pp 1692–1701 | Cite as

Regulation of Glycogen Content in Astrocytes via Cav-1/PTEN/AKT/GSK-3β Pathway by Three Anti-bipolar Drugs

  • Shu Jia
  • Baoman Li
  • Jingyang Huang
  • Alexei Verkhratsky
  • Liang Peng
Original Paper
  • 93 Downloads

Abstract

Here we present the data indicating that chronic treatment with three antibipolar drugs, lithium, carbamazepine and valproic acid regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultured astrocytes. All three drugs down-regulate gene expression of Caveoline 1 (Cav-1), decrease membrane content of phosphatase and tensin homolog (PTEN), increase activity of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and serine-threonine kinase (AKT), and elevate glycogen synthase kinase 3β (GSK-3β) phosphorylation thus suppressing its activity. As expected, treatment with any of these three drugs increases glycogen content in astrocytes. Our findings indicate that regulation of glycogen content via Cav-1/PTEN/AKT/GSK-3β pathway by the three anti-bipoar drugs may be responsible for therapeutic effects of these drugs, and Cav-1 is an important signal element that may contribute to pathogenesis of various CNS diseases and regulation of its gene expression may be one of the underlying mechanisms of drug action for antibipolar drugs and antidepressants currently in clinical use.

Keywords

Biporlar disorder Cav-1 PTEN PI3K/AKT GSK-3β Glycogen 

Notes

Acknowledgements

This study was supported by Grant Nos. 201602834 from the Natural Science Foundation of Liaoning Province and [2015]1098 from the Scientific Research Foundation for Overseas Scholars of Education Ministry of China to BL.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Metabolic Brain Diseases, Institute of Metabolic Disease Research and Drug DevelopmentChina Medical UniversityShenyangPeople’s Republic of China
  2. 2.Department of Laboratory Medicine & Pathology in the Faculty of Medicine and DentistryUniversity of AlbertaEdmontonCanada
  3. 3.Faculty of Life ScienceThe University of ManchesterManchesterUK
  4. 4.Achucarro Center for NeuroscienceIKERBASQUE, Basque Foundation for ScienceBilbaoSpain

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