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Increased phosphorylation of Ser473-Akt, Ser9-GSK-3beta and Ser133-CREB in the rat frontal cortex after MK-801 intraperitoneal injection

Cited 34 time in Web of Science Cited 35 time in Scopus
Authors
Ahn, Yong Min; Seo, Myoung Suk; Kim, Se Hyun; Kim, Yeni; Yoon, Se Chang; Juhnn, Yong-Sung; Kim, Yong Sik
Issue Date
2005-05-10
Publisher
Cambridge University Press
Citation
Int J Neuropsychopharmacol. 2005 Dec;8(4):607-13. Epub 2005 May 9.
Keywords
Actins/metabolismAnimalsBlotting, WesternCatenins/metabolismCyclic AMP Response Element-Binding Protein/*metabolismDizocilpine Maleate/administration & dosage/*pharmacologyDose-Response Relationship, DrugExcitatory Amino Acid Antagonists/administration & dosage/*pharmacologyGlycogen Synthase Kinase 3/*metabolismInjections, IntraperitonealMalePhosphorylationPrefrontal Cortex/drug effects/*metabolismProto-Oncogene Proteins c-akt/*metabolismRatsRats, Sprague-DawleySerine/*metabolism
Abstract
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.
ISSN
1461-1457 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15877933

http://hdl.handle.net/10371/29013
DOI
https://doi.org/10.1017/S1461145705005353
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College of Medicine/School of Medicine (의과대학/대학원)Psychiatry (정신과학전공)Journal Papers (저널논문_정신과학전공)
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