S-Space College of Medicine/School of Medicine (의과대학/대학원) Psychiatry (정신과학전공) Journal Papers (저널논문_정신과학전공)
The effect of MK-801 on mTOR/p70S6K and translation-related proteins in rat frontal cortex
- Issue Date
- Neurosci Lett. 2008 21;434(1):23-8.
- Animals ; Dizocilpine Maleate/*pharmacology ; Eukaryotic Initiation Factor-4E/biosynthesis/drug effects/genetics ; Excitatory Amino Acid Antagonists/pharmacology ; Gene Expression Regulation/drug effects/physiology ; Glutamic Acid/metabolism ; Hallucinogens/pharmacology ; Nerve Tissue Proteins/biosynthesis/genetics ; Phosphorylation/drug effects ; Prefrontal Cortex/*drug effects/metabolism ; Protein Biosynthesis/*drug effects/genetics ; Protein Kinases/biosynthesis/*drug effects/genetics ; Proto-Oncogene Proteins c-akt/drug effects/metabolism ; RNA, Messenger/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Ribosomal Protein S6 Kinases, 70-kDa/biosynthesis/*drug effects/genetics ; Signal Transduction/drug effects/physiology ; Transcriptional Activation/drug effects/physiology ; Up-Regulation/drug effects/physiology
- In experimental animals, including rats, MK-801 produces characteristic behavioural changes that model schizophrenia. It has been hypothesized that these changes accompany long-term synaptic changes, which require protein neosynthesis. We observed the effect of MK-801 on the "mammalian target of rapamycin" (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway that regulates protein synthesis in the rat frontal cortex. A single injection of MK-801 (0.5, 1, or 2mg/kg) induced an acute increase in the phosphorylation of Akt (Ser-473) eIF4E-binding protein (4E-BP1) (Thr-37/46) and p70S6K (Thr-389). In contrast, after repeated treatment with MK-801 (1mg/kg for 5 or 10 days), the phosphorylation of Akt (Ser-473), mTOR (Ser-2481), 4E-BP1 (Thr-37/46), p70S6K (Thr-389), and S6 (Ser-240/244) increased. Thus, proteins in the mTOR/p70S6K pathway are modulated in chronic MK-801 animal models. These findings may suggest that repeated MK-801 treatment activates the signal transduction pathways involved in the initiation of protein synthesis in the rat frontal cortex.
- 0304-3940 (Print)
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