Literature DB >> 18262357

The effect of MK-801 on mTOR/p70S6K and translation-related proteins in rat frontal cortex.

Se Chang Yoon1, Myoung Suk Seo, Se Hyun Kim, Won Je Jeon, Yong Min Ahn, Ung Gu Kang, Yong Sik Kim.   

Abstract

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.

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Year:  2008        PMID: 18262357     DOI: 10.1016/j.neulet.2008.01.020

Source DB:  PubMed          Journal:  Neurosci Lett        ISSN: 0304-3940            Impact factor:   3.046


  15 in total

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