| Title | Desipramine prevents stress-induced changes in depressive-like behavior and hippocampal markers of neuroprotection. | | Author(s) | Bravo JA, Díaz-Veliz G, Mora S, Ulloa JL, Berthoud VM, Morales P, Arancibia S, Fiedler JL | | Institution | aLaboratory of Neuroplasticity and Neurogenetics, Department of Biochemistry and Molecular Biology, Faculty of Chemistry and Pharmaceutical Sciences bICBM, School of Medicine, Universidad de Chile, Santiago, Chile cDepartment of Pediatrics, University of Chicago, Chicago, Illinois, USA dMolecular Mechanisms in Neurodegenerative Dementia Laboratory, Inserm, University of Montpellier 2, EPHE, Montpellier, France. | | Source | Behav Pharmacol 2009 May 6. | | Abstract | Extracellular signal-regulated kinases (ERKs) are widely implicated in multiple physiological processes. Although ERK1/2 has been proposed as a common mediator of antidepressant action in naive rodents, it remains to be determined whether the ERK1/2 pathway plays a role in depressive disorder. Here, we investigated whether chronic restraint stress (14 days) and antidepressant treatment [desipramine (DMI), 10 mg/kg intraperitoneally] induce changes in animal behavior and hippocampal levels of phospho-ERK1/2 and its substrate phospho-cAMP response element-binding protein (CREB). The results indicated that stress-induced depressive-like behaviors were correlated with an increase in P-ERK1/2 and P-CREB in the hippocampus evaluated by immunoblot analysis. As an indication of CREB activity, we evaluated changes in mRNA levels of its target genes. Brain-derived neurotrophic factor (BDNF) mRNA was reduced by stress, an effect prevented by DMI only in the CA3 area of hippocampus. Bcl-2 mRNA was reduced in all hippocampal regions by stress, an effect independent of DMI treatment. However, immunoblot from hippocampal extracts revealed that stress increased BCL-2 levels, an effect prevented by chronic DMI. These results suggest that ERKs and BDNF may be altered in depressive disorder, modifications that are sensitive to DMI action. In contrast, the stress-induced increase in BCL-2 may correspond to a neuroprotective response. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19424057 |
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