1. Antidepressants activate CaMKII in neuron cell body by Thr286 phosphorylation
- Author
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Maurizio Popoli, Andrea de Bartolomeis, Giordano D’Urso, Alessandro Barbon, Giorgio Racagni, R. Giambelli, Antonio Galietta, Ettore Tiraboschi, Massimo Gennarelli, Sergio Barlati, Tiraboschi, E, Giambelli, R, D'Urso, Giordano, Galietta, A, Barbon, A, DE BARTOLOMEIS, Andrea, Gennarelli, M, Barlati, S, Racagni, G, and Popoli, M.
- Subjects
Male ,Threonine ,medicine.medical_specialty ,Time Factors ,Thr286 phosphorylation ,Morpholines ,Blotting, Western ,Antidepressant ,Pharmacology ,Biology ,Hippocampus ,Drug Administration Schedule ,Rats, Sprague-Dawley ,Reboxetine ,Internal medicine ,Desipramine ,Ca2+/calmodulin-dependent protein kinase ,medicine ,Animals ,ASK1 ,RNA, Messenger ,Phosphorylation ,Cells, Cultured ,In Situ Hybridization ,Neurons ,Analysis of Variance ,CaMKII ,Dose-Response Relationship, Drug ,Kinase ,General Neuroscience ,Cyclin-dependent kinase 5 ,Immunohistochemistry ,Antidepressive Agents ,Rats ,Enzyme Activation ,Endocrinology ,Synaptic plasticity ,Calcium-Calmodulin-Dependent Protein Kinases ,Calcium ,Calcium-Calmodulin-Dependent Protein Kinase Type 2 ,medicine.drug - Abstract
CaM kinase II, a regulator of synaptic plasticity, is implicated in pathophysiology and pharmacology of psychiatric disorders. Chronic treatment with antidepressants desipramine and reboxetine up-regulated CaM kinase II in neuronal cell bodies of hippocampus. mRNA/protein expression for αCaM kinase II was unchanged, whereas Thr 286 phosphorylation was increased in pyramidal/granular cell bodies, suggesting that increased phosphorylation is responsible for kinase activation. Short-term treatment of neuronal cultures with reboxetine reduced kinase activation in a concentration-dependent manner. The short-term inhibitory effect of reboxetine suggests that kinase up-regulation during antidepressant drug treatment is an adaptive response compensating for initial functional down-regulation.
- Published
- 2005