Reciprocal regulation of neuronal activity by s-nitrosylation and S-PALMITOYLATION
| Grant number: | 11/20762-7 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | June 01, 2012 |
| Effective date (End): | September 30, 2015 |
| Field of knowledge: | Biological Sciences - Pharmacology |
| Principal Investigator: | Leonardo Resstel Barbosa Moraes |
| Grantee: | Alessandra das Graças Fedoce |
| Home 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 |
Abstract 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. | |