Involvement of BDNF-TrkB signaling in the antidepressant-like effects of the nitric oxide in the frontal cortex

• Grant number: 13/13223-8
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2013
• End date: September 30, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Sâmia Regiane Lourenço Joca
• Grantee: Caroline Biojone
• Supervisor: Eero Hemminki Castrén
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Helsinki, Finland
• Associated to the scholarship: 12/23087-1 - Role of epigenetics mechanisms in the antidepressant-like effects of the nitric oxide in the frontal cortex, BP.PD

Abstract

There is evidence indicating that L-arginine (a nitric oxide synthase substrate) administration induces biphasic effects in the forced swimming test. It suggests that nitric oxide could induce both antidepressant- and depressive-like effects. Moreover, our group has demonstrated that transgenic mice that present increased nitric oxide production in the frontal cortex present antidepressant-like phenotype. However, in the last years only the antidepressant-like effect of NOS inhibition has been investigated. Recently, the Antonella Riccio's group has reported, in cortical neurons in vitro, that nitric oxide is able to increase the expression of CREB-regulated genes through epigenetic mechanisms. CREB also modulates the expression of BDNF (a neurotrophin that plays a crucial role mediating the antidepressant effect), so the present study aims investigate in vivo and in vitro whether the antidepressant-like effect induced by nitric oxide is due to increased BDNF expression, and also whether the same epigenetic mechanisms described by Riccio (it means, nitrosylation of histone deacetilase and consequent increased in the acetylation of BDNF promoter gene) are involved in this phenomenon. (AU)