Schizophrenia is a severely incapacitating mental disorder. It's expressed in the late adolescence / early adulthood and causes severe damage on cognitive and social performances of the pacients, as well as great suffering for their families. Its pathophysiology remains unclear, but changes on BDNF (brain-derived neutrophic factor) seem to be associated. The treatment is performed with antipsychotics, although they represent a breakthrough of psychopharmacology, do not benefit all patients. Even those who benefit may suffer relapses, which are associated with worsening of the disease, and development of severe side effects. Thus, the search for potential preventive interventions is extremely important. Considering the methodological and ethical difficulties arising from the study of individuals at high risk to develop schizophrenia, the use of animal models becomes necessary.Based on the SHR strain's behavioral, pharmacological and neurochemical profile, our group has suggested that it can be used as a good model for investigating several aspects of schizophrenia. Thus, this project has a main objective of investigating possible changes in brain and peripheral levels of BDNF (pro-BDNF and mature BDNF analyzed separately) and its receptors (TrkB and p75) in the SHR strain at different ages. These measurements can contribute to the understanding of the pathophysiology of schizophrenia and to identify possible development biomarkers.In parallel, our group is investigating the potential preventive interventions for the development of schizophrenia. These interventions (pharmacological or environmental) are studied in the SHR strain and applied in young animals. Their potential benefits are assessed in adulthood. Thus, as the second goal, we intend to evaluate the possible beneficial effects of an early and prolonged exposure to an enriched environment (able to increase levels of BDNF) or a long-term treatment with antipsychotics on the behavioral changes associated with schizophrenia in the SHR strain, and the involvement of BDNF and its receptor in these effects.
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