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

Grant number: 13/13223-8
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): October 01, 2013
Effective date (End): September 30, 2014
Field of knowledge:Biological Sciences - Pharmacology - Neuropsychopharmacology
Principal researcher:Sâmia Regiane Lourenço Joca
Grantee:Caroline Biojone
Supervisor abroad: Eero Hemminki Castrén
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: 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


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)

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