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Reduced CREB phosphorylation after chronic lithium treatment is associated with down-regulation of CaM kinase IV in rat hippocampus.
- Source :
-
The international journal of neuropsychopharmacology [Int J Neuropsychopharmacol] 2007 Aug; Vol. 10 (4), pp. 491-6. Date of Electronic Publication: 2006 Aug 21. - Publication Year :
- 2007
-
Abstract
- Lithium is widely used in the treatment of bipolar disorder, although its mechanism of action is not fully clear. This study was undertaken to assess the effects of prolonged lithium administration on cAMP responsive element-binding protein (CREB) phosphorylation and CaM kinase IV (CaMKIV), one of the main kinases phosphorylating CREB in neurons following synaptic activation. CREB total protein expression and phosphorylation (Ser133), as well as CaMKIV enzymatic activity, phosphorylation of Thr196 (the activator residue) and kinase expression level were assessed in total homogenates and nuclei from the hippocampus and prefrontal/frontal cortex following 5 wk lithium treatment. Whereas no significant effects were found in prefrontal/frontal cortex, lithium administration reduced CREB phosphorylation and at the same time down-regulated CaMKIV (enzymatic activity, phospho-Thr196 and protein expression level) in cell nuclei from the hippocampus. These data suggest for the first time the involvement of CaMKIV in the mechanism of action of lithium.
- Subjects :
- Animals
Calcium-Calmodulin-Dependent Protein Kinase Type 4
Cell Nucleus drug effects
Cell Nucleus metabolism
Down-Regulation
Hippocampus enzymology
Hippocampus metabolism
Male
Phosphorylation
Prefrontal Cortex enzymology
Prefrontal Cortex metabolism
Rats
Rats, Sprague-Dawley
Time Factors
Antimanic Agents pharmacology
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Cyclic AMP Response Element-Binding Protein metabolism
Hippocampus drug effects
Lithium Carbonate pharmacology
Prefrontal Cortex drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1461-1457
- Volume :
- 10
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The international journal of neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 16923323
- Full Text :
- https://doi.org/10.1017/S1461145706007140