Regulation of Phosphodiesterase-4 (Pde4) Expression in Mouse Brain by Repeated Antidepressant Treatment: Comparison with Rolipram.
From: Department of Behavioral Medicine & Psychiatry, West Virginia University Health Sciences Center, Morgantown, 26506-9128, USA.
Brain research
- Publish Date: Jun 2006
- ISSN: 0006-8993
- Volume: 1096
- Issue: 1
- Pages: 104-12
- Medium: Print
- Language: English
- Citation (JAMA): Dlaboga Daniel, Hajjhussein Hassan, O'Donnell James M, et al. Regulation of Phosphodiesterase-4 (Pde4) Expression in Mouse Brain by Repeated Antidepressant Treatment: Comparison with Rolipram.. Brain Res. Jun 2006;1096:104-12
Abstract
Cyclic nucleotide phosphodiesterase-4 (PDE4) is a component of signaling pathways involved in the mediation of antidepressant activity. Of the four PDE4 subtypes, PDE4D appears to be of particular importance, given the finding that PDE4D-deficient mice exhibit an antidepressant-like behavioral phenotype. In mouse hippocampus and cerebral cortex, the effects of repeated treatment with the antidepressants desipramine and fluoxetine or the PDE4 inhibitor rolipram on the expression of PDE4D was compared to that of PDE4A and PDE4B, the other two subtypes expressed in the brain. Expression of PDE4D was increased by all drugs tested, with the exception of desipramine in hippocampus. By contrast, these treatments affected PDE4A and PDE4B expression differentially. In hippocampus, antidepressants increased PDE4A and decreased PDE4B, whereas ROL decreased PDE4A and did not change PDE4B. In cerebral cortex, antidepressants increased PDE4A and did not change PDE4B, whereas ROL did not change PDE4A and increased PDE4B. 3H-Rolipram binding was increased in cytosolic, but not in membrane, fractions of cerebral cortex by all drugs tested; there were no changes observed in hippocampus. Overall, the present results suggest some species-dependence of the regulation of PDE4 subtypes, based on data obtained previously using rats. They also suggest that the PDE4D subtype may be of particular importance as an antidepressant target in that it is regulated by repeated treatment with both norepinephrine and serotonin reuptake inhibitors as well as by the PDE4 inhibitor rolipram, drugs that produce antidepressant effects via different neuropharmacological mechanisms.
Mesh Headings (Keywords): 3’,5’-Cyclic-AMP Phosphodiesterases, Adrenergic Uptake Inhibitors, Animals, Antidepressive Agents, Brain, COS Cells, Cercopithecus aethiops, Cerebral Cortex, Cyclic Nucleotide Phosphodiesterases, Type 4, Cytosol, Electrophoresis, Polyacrylamide Gel, Hippocampus, Immunohistochemistry, Isoenzymes, Male, Membranes, Mice, Mice, Inbred ICR, Rolipram, Serotonin Uptake Inhibitors
Check for Full Text / PubMed Unique Identifier (PMID): 16730340
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.