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Santos LA. Susceptibility and resilience to the effects of prolonged social defeat in adolescent male mice: a study of BDNF in the brain. [Masters thesis (Pharmacology)]. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo; 2014. The depressive disorders, or depression, are the third major cause of disability and years of life lost in the world. However, the treatment for depression is still deficient and it doesn ́t cater to the clinical necessity, stressing the urgency for new studies related to this field. The stress stands out as one of the main precipitant factor of depression. Accordingly, adolescence is a stressful period in the human life, where many changes at the hormonal and social levels of an individual occur. The stress during adolescence which is more prevalent is of social nature, specially the bullying, is thought to be a major stressor that can lead to psychiatry disorders. Many animal models of depression use the prolonged social stress as a tool to induce behavior changes similar to those observed in depressed patients. New studies involving humans and animal models of depression showed alterations related to neuroplasticity issues participating on the neurobiology of depression, being the brain derived neurotrophic factor (BDNF) one of most important molecule involved. However, little is known about the effects of prolonged social stress during adolescence. In this context, we use an animal model of prolonged social defeat, in adolescent male C57BL/6 mice, to evaluate the effects of prolonged social stress on emotional behaviors, and on gene and protein expression of BDNF and its different isoforms in prefrontal cortex, hippocampus and dorsal striatum. Our model was able to induce anhedonia in the sucrose preference test and social avoidance in the social interaction test in defeated animals. Our behavioral data analyses allowed us to identify a subgroup that was susceptible to the effects of stress, which showed anhedonia, and another subgroup resilient to these effects. Defeated animals exhibited anxiety-like behaviors in one set of animals, but these changes in behavior didn ́t repeat along the other sets. Likewise, only one set showed decrease weight gain in the experiment. Moreover, these parameters weren ́t correlated with resilience and susceptibility to the stress. We couldn ́t detect a change in serum corticosterona levels in defeat mice. Our molecular analyses showed that the susceptible animals had a reduction in the transcript Bdnf4 expression and in the protein levels of total BDNF and its truncated isoform in dorsal striatum, an area that is low correlated to depression. Curiously, no changes were seen in prefrontal cortex and hippocampus, brain areas usually related to depression. Concluding, our data show that prolonged psychological stress is capable of inducing emotional alterations in adolescent male C57BL/6 mice related to depressive behaviors and social avoidance, and related to specific changes in gene and protein expression of BDNF in dorsal striatum, suggesting an important role for this area in depression and molecular expression profiles possibly related to resilience and susceptibility to the effects of prolonged social defeat.

Suscetibilidade e resiliência aos efeitos da subjugação social prolongada em camundongos machos adolescentes: estudo do BDNF cerebral.