Involvement of BDNF-TrkB-mTOR pathway in the antidepressant-like effect induced by nos inhibitors

• Grant number: 13/00916-5
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date until: April 25, 2013
• End date until: August 24, 2013
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Sâmia Regiane Lourenço Joca
• Grantee: Vitor Silva Pereira
• Supervisor: Gregers Wegener
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Aarhus University, Denmark
• Associated to the scholarship: 11/13899-6 - Role of ventro medial prefrontal cortex NMDA-NO pathway in the modulation of behavioural consequences elicited by forced swim stress: intracellular mechanisms, BP.DR

Abstract

Several data suggest the participation of glutamatergic and nitrergic systems in the neurobiology of depression. The administration of glutamatergic antagonists (ketamine) or nitric oxide (NO) inhibitors (7-NI) in animals induces antidepressant-like effects. The effects of ketamine seem to be dependent of neural plasticity mechanisms, because the injection of protein synthesis inhibitor can block the antidepressant-like effects of ketamine. Recent works show that the effects of ketamine and 7-NI are also dependent of intracellular pathways involved in neural plasticity, such as BDNF-TrkB-mTOR pathway. The ventromedial prefrontal cortex (vMPFC) is one of the main structures involved on behavioral control and the glutamatergic neurotransmission of this structure has received considerable attention in the study of depression. Therefore, the aim of this work is to test the hypothesis that the antidepressant-like effects induced by inhibition of NO synthesis would involve the modulation of BDNF levels in the vMPFC, with subsequent activation of its receptor, TrkB, and mTOR. These will be investigated by means of analysis of gene and protein expression in the MPFC of rats treated with Ketamine, 7-NI (nNOS inhibitor) or Aminoguanidine (NOS inhibitor), and submitted to animal models of depression. We will also investigate whether treatment with these drugs can alter the function of BDNF-TrkB-mTOR pathway in the vMPFC of Flinders Sensitive Line (FSL) rats. The FSL rats are known as a genetic animal model of depression because they express some features of human major depression, such as elevated REM sleep and swim test immobility. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PEREIRA, VITOR SILVA; ELFVING, BETINA; JOCA, SAMIA R. L.; WEGENER, GREGERS. Ketamine and aminoguanidine differentially affect Bdnf and Mtor gene expression in the prefrontal cortex of adult male rats. European Journal of Pharmacology, v. 815, p. 304-311, NOV 15 2017. (13/00916-5)