Summary.
Protein phosphatase 2A (PP2A) regulates protein kinase cascades and thus plays an important role in the regulation of cell growth, gene expression and development. We examined the influence of lithium and valproate on the expression of PP2A and its serine/threonine phosphatase activity in the rat frontal cortex and hippocampus. Western blot and immunohistochemical analyses demonstrated that neither lithium nor valproate treatment had an effect on the levels of PP2A immunoreactivity in these brain regions. However, administration of lithium for 1 or 14 days significantly upregulated the activity of PP2A in the frontal cortex. Similarly, lithium administration tended to increase the activity of PP2A in the hippocampus. In contrast, neither a single nor repeated administration of valproate affected the activity of PP2A in these brain regions. These findings indicate that lithium, but not valproate, upregulated the activity of PP2A in the rat brain. It is suggested that the changes in neuronal functions induced by PP2A may be, at least in part, associated with the therapeutic action of lithium.
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Received September 9, 2002; accepted October 22, 2002 Published online December 16, 2002
Acknowledgements We thank Dr. J. Takahashi (Department of Psychiatry, Shiga University of Medical Sciences), Dr. M. Endo and Ms S. Endo (Department of Pharmacology, Yamagata University, School of Medicine), and Dr. T. Fukumoto and Ms M. Okamura (Department of Psychiatry and Neurosciences, Graduate School of Biomedical Sciences, Hiroshima University) for their help throughout this study.
Authors' address: S. Yamawaki, M.D., Ph.D., Department of Psychiatry and Neurosciences, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan, e-mail: yamawaki@hiroshima-u.ac.jp
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Tsuji, S., Morinobu, S., Tanaka, K. et al. Lithium, but not valproate, induces the serine/threonine phosphatase activity of protein phosphatase 2A in the rat brain, without affecting its expression. J Neural Transm 110, 413–425 (2003). https://doi.org/10.1007/s00702-002-0798-0
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DOI: https://doi.org/10.1007/s00702-002-0798-0