Regulation of Glycogen Content in Astrocytes via Cav-1/PTEN/AKT/GSK-3β Pathway by Three Anti-bipolar Drugs.
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.
['Jia|Shu|S|', 'Li|Baoman|B|', 'Huang|Jingyang|J|', 'Verkhratsky|Alexei|A|', 'Peng|Liang|L|']
D000818:Animals D000831:Animals, Newborn D018692:Antimanic Agents D001253:Astrocytes D001714:Bipolar Disorder D002220:Carbamazepine D051242:Caveolin 1 D002478:Cells, Cultured D004305:Dose-Response Relationship, Drug D006003:Glycogen D000071679:Glycogen Synthase Kinase 3 beta D008094:Lithium D051379:Mice D051059:PTEN Phosphohydrolase D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction D014635:Valproic Acid
Glycogen Cav-1 PTEN GSK-3β PI3K/AKT Biporlar disorder