Increased phosphorylation of Ser473-Akt, Ser9-GSK-3beta and Ser133-CREB in the rat frontal cortex after MK-801 intraperitoneal injection.
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.
Ahn
Yong Min
YM
Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, Korea.
Seo
Myoung Suk
MS
Kim
Se Hyun
SH
Kim
Yeni
Y
Yoon
Se Chang
SC
Juhnn
Yong-Sung
YS
Kim
Yong Sik
YS
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D051177:Catenins / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D007274:Injections, Intraperitoneal; D008297:Male; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012694:Serine / Q000378:metabolism*
D000199:Actins; D051177:Catenins; D017362:Cyclic AMP Response Element-Binding Protein; D018691:Excitatory Amino Acid Antagonists; D012694:Serine; D016291:Dizocilpine Maleate; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3