S-Space College of Medicine/School of Medicine (의과대학/대학원) Psychiatry (정신과학전공) Journal Papers (저널논문_정신과학전공)
Increased phosphorylation of Ser473-Akt, Ser9-GSK-3beta and Ser133-CREB in the rat frontal cortex after MK-801 intraperitoneal injection
- Ahn, Yong Min; Seo, Myoung Suk; Kim, Se Hyun; Kim, Yeni; Yoon, Se Chang; Juhnn, Yong-Sung; Kim, Yong Sik
- Issue Date
- Cambridge University Press
- Int J Neuropsychopharmacol. 2005 Dec;8(4):607-13. Epub 2005 May 9.
- Actins/metabolism; Animals; Blotting, Western; Catenins/metabolism; Cyclic AMP Response Element-Binding Protein/*metabolism; Dizocilpine Maleate/administration & dosage/*pharmacology; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists/administration & dosage/*pharmacology; Glycogen Synthase Kinase 3/*metabolism; Injections, Intraperitoneal; Male; Phosphorylation; Prefrontal Cortex/drug effects/*metabolism; Proto-Oncogene Proteins c-akt/*metabolism; Rats; Rats, Sprague-Dawley; Serine/*metabolism
- GSK-3beta is regarded as playing an important part in the pathogenesis of schizophrenia and the action of psychotomimetic agents. We observed phosphorylation of molecules associated with the GSK-3beta signalling pathway in the rat brain after MK-801 injection, which induces a schizophrenia-like state in humans. Ser9-GSK-3beta phosphorylation was increased after injection of 1 mg/kg MK-801 in the rat frontal cortex but not in the hippocampus or cerebellum. This increase peaked at 30 min and was maintained until 90 min after injection. The phosphorylation showed a dose-dependent increase up to 1 mg/kg MK-801, followed by a decrease at higher dosage. Furthermore, phosphorylation of Ser473-Akt and Ser133-CREB showed similar temporal, dose-dependent and regionally specific patterns with those of Ser9-GSK-3beta. However, phosphorylation of Dvl and Ser33-beta-catenin was not affected by MK-801. These results suggest that GSK-3beta phosphorylation by MK-801 may be associated with the Akt-GSK-3beta pathway rather than with the Wnt-Dvl-GSK3beta pathway.
- 1461-1457 (Print)