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Possible involvement of oxidative/nitrosative stress induced by restraint stress in modulation of conditioned emotional response

Grant number: 11/20762-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2012
Effective date (End): September 30, 2015
Field of knowledge:Biological Sciences - Pharmacology - General Pharmacology
Principal Investigator:Leonardo Resstel Barbosa Moraes
Grantee:Alessandra das Graças Fedoce
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):14/02135-3 - Reciprocal regulation of neuronal activity by s-nitrosylation and S-PALMITOYLATION, BE.EP.DR


The stress is a risk factor for the development of affective disorders, such as anxiety and depression. The body's response to stress leads to both neurochemical and behavioral changes which can be associated with excessive production of reactive oxygen species (ROS), oxidative stress and reactive nitrogen species (RNS), nitrosative stress. Several animal models can exert influence in the pro-oxidant/antioxidant balance, by raising the concentrations of ROS/RNS. One of them is the restraint stress, which is a model of acute and inescapable stress which evokes behavioral, autonomic and hormonal alterations and neuronal damage in some brain areas, such as the prefrontal cortex (PFC) and hippocampus (HIP). These structures are part of the limbic system and are involved with modulation of autonomic and behavioral responses during stress situations. It was recently demonstrated a correlation between oxidative stress and a number of metabolic disorders which could be associated with anxiogenic-like effects observed in animals submitted to experimental models of anxiety. Thereby, the brain is very susceptible to these species for having high oxidative metabolism, modest antioxidant defenses and a rich constitution of lipids that makes it highly susceptible to lipid peroxidation. Thus, the present project will investigate whether the restraint stress can influence the redox state in the PFC and HIPP. Moreover, it will study the effects of stress on behavioral and autonomic responses (conditioned emotional response-CER) subsequently evaluated in an experimental model of anxiety and learned fear, the contextual fear conditioning (CFC). The oxidative/ nitrosative parameters will be evaluated after the restraint stress procedure or after the evaluation of the REC by changes in the activities of superoxide dismutase and glutathione peroxidase, by measurement of nitrites and nitrates, for verification of protein carboxylation and lipid peroxidation. A better understanding of such mechanisms may allow the development of more effective pharmacological interventions than the currently used.

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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)
FERREIRA-JUNIOR, NILSON C.; FEDOCE, ALESSANDRA G.; ALVES, FERNANDO H. F.; RESSTEL, LEONARDO B. M.. Medial prefrontal cortex N-methyl-D-aspartate receptor/nitric oxide/cyclic guanosine monophosphate pathway modulates both tachycardic and bradycardic baroreflex responses. Journal of Neuroscience Research, v. 91, n. 10, p. 1338-1348, . (11/07332-3, 11/20762-7, 10/09462-9, 11/19494-8)
BORELLI, KARINA G.; ALBRECHET-SOUZA, LUCAS; FEDOCE, ALESSANDRA G.; FABRI, DENISE S.; RESSTEL, LEONARDO B.; BRANDAO, MARCUS L.. Conditioned fear is modulated by CRF mechanisms in the periaqueductal gray columns. Hormones and Behavior, v. 63, n. 5, p. 791-799, . (11/20762-7, 11/07332-3, 11/00041-3, 12/09300-4)

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