title: Bi-phasic regulation of glycogen content in astrocytes via Cav-1/PTEN/PI3K/AKT/GSK-3β pathway by fluoxetine.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Qiufang
authors.initials: Q
authors.lastname: Bai
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Gu
authors.affiliation: Faculty of Life Science, The University of Manchester, Manchester, UK.|Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain.
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
authors.affiliation: 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. sharkfin039@163.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Peng
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D051242:Caveolin 1 / Q000187:drug effects*; D058534:Class I Phosphatidylinositol 3-Kinases; D005473:Fluoxetine / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006003:Glycogen / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000187:drug effects*; D051379:Mice; D051059:PTEN Phosphohydrolase / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects*; D010766:Phosphorylation; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051242:Caveolin 1; D058534:Class I Phosphatidylinositol 3-Kinases; D005473:Fluoxetine; D006003:Glycogen; D000071679:Glycogen Synthase Kinase 3 beta; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D034741:RNA, Small Interfering; D017367:Selective Serotonin Reuptake Inhibitors; C495541:Cav1 protein, mouse; C421683:Pik3cd protein, mouse; C487757:Pten protein, mouse
keywords: Cav-1; Fluoxetine; GSK-3β; Glycogen; PI3K/AKT; PTEN