Evaluation of the role of molecular targets in the neurobiology of depressive disorder using interference RNA

• Grant number: 09/11220-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2010
• End date: December 31, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Frederico Rogério Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 07/03685-3 - Typical and atypical neurotransmitters in neuropsychiatric disorders, AP.TEM
• Associated scholarship(s): 12/04199-3 - Evaluation of effects of chronic treatment with 7-nitroindazole, a preferential neuronial nitric oxid synthase inhibitor, on system Calcium-calmodulins signalization in hipocampus neurons, BE.EP.PD

Abstract

Major depressive disorder was ranked as the fourth greatest cause of global illness burden, and projections indicate that by 2020 it will become the second leading cause of disease worldwide, occupying the first position among psychiatric disorders. Despite advances obtained on depression treatment, remission rate is frequently not higher then 50%. Therefore, the development of more efficient antidepressant drugs is still necessary. The antidepressant-like effects of neuronal nitric oxide synthase inhibition or antagonism of glutamate-mediated neurotransmission indicates that the glutamatergic-nitrergic system can play an important role in this disorder. Changes in the expression of specific genes, particularly those related to adaptation to the stressful stimuli, have been proposed as a possible mechanism to explain the effects of antidepressant treatments. Previous studies from our laboratory have showed that the antidepressant-like effects observed after chronic treatment with imipramine or a neuronial nitric oxide synthase inhibitor are associated to modification of expression of several genes on hippocampus, including the calmodulin 1, cannabinoid receptor 1, synaptofisin and glutathione peroxidase (FERREIRA et al., 2008b). Thus, the aim of this project is investigate whether the manipulation of these genes by using interference RNA could block the antidepressant effect promoted by those drugs on the forced swimming test model.