Electroconvulsive seizures increase the expression of MAP kinase phosphatases in limbic regions of rat brain.
The mitogen-activated protein (MAP) kinase cascades regulate a variety of cellular activities, including cell growth, proliferation, and apoptosis, and are reported to play a role in the actions of antidepressant treatment. There are a number of different classes of protein phosphatases that could influence the MAP kinase cascade. One of these, the MAP kinase phosphatase (MKP) family, is known to play a key role in dephosphorylation of activated MAP kinase. In the present study, we analyzed the expression of the MKP1, MKP2, and MKP3 isoforms in rat brain after electroconvulsive seizure (ECS), considered the most effective treatment for depression. In situ hybridization analysis demonstrates that ECS differentially regulates the expression of the MKP isoforms. Expression of MKP1 mRNA is robustly increased by acute ECS in the major cell layers of the hippocampus, including the dentate gyrus granule cell layer and the CA1 and CA3 pyramidal cell layers. In contrast, MKP2 is induced mainly in the dentate gyrus and MKP3 is preferentially increased in the CA1 and CA3 cell layers. In the prefrontal cortex, all three MKP isoforms are upregulated by acute ECS administration. Chronic ECS resulted in a similar pattern of induction for each of the MKP subtypes, demonstrating that there is little or no desensitization of the response to repeated ECS. The induction of MKP expression serves as negative feedback control for the MAP kinase cascades. Upregulation of MKP expression could dampen the actions of ECS, indicating that blockade of the MKPs could enhance the actions of antidepressant treatment.
Kodama
Masafumi
M
Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT 06508, USA.
Russell
David S
DS
Duman
Ronald S
RS
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D015153:Blotting, Western; D004597:Electroshock; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008032:Limbic System / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D015345:Oligonucleotide Probes / Q000138:chemical synthesis; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis* / Q000235:genetics; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000928:Antidepressive Agents; D007527:Isoenzymes; D015345:Oligonucleotide Probes; D012313:RNA; D017027:Protein Tyrosine Phosphatases