Evaluation of the BDNF role on the antidepressant-like effects produced by inhibition of the nitric oxide production

• Grant number: 08/10267-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2009
• End date: February 28, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Francisco Silveira Guimaraes
• Grantee: Caroline Biojone
• 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

Abstract

Several studies have investigated the neurobiology of depression. However, that is a complex theme and important questions remain unclear. Nowadays, the investigation of new factors that can be involved in this disturb have elucidated some aspects. Several pieces of evidence suggest that nitric oxide could be involved in the genesis of depression. Nitric oxide synthase inhibition produces antidepressant-like effects whereas stress can increased nitric oxide synthase expression in HPA axis, for example. Some studies have reported association between brain derived neurotrophic factor (BDNF, the most abundant neurotrophin in the brain) and depression. BDNF injection into the hippocampus produces antidepressant-like effects; pharmacological treatment with antidepressant drugs can increase BDNF levels whereas stress can decrease it. Besides, evidence indicated that neuronal death in the hippocampus and a decrease in volume of this structure is associated with stress. Altogether, these data suggest that stress, nitric oxide, BNDF and neuronal death could mediate the onset of depression. This association has not been investigated yet. So, the present study aim is to evaluate the effects of footshock stress (learned helplessness model) on behavioral deficits, BDNF levels and neuronal death in the hippocampus. We will also investigated if these effects could be prevented by nitric oxide synthase inhibition or by BDNF i.c.v. administration. (AU)