Women are twice as likely as men to experience depression in their lives, yet the reasons for this sex difference in mental illness are unknown. Recently it has been proposed that neurogenesis, the production of new neurons in the adult brain is involved i n the expression of major depression, although the studies have only been conducted in males. In this project, the research fellow will examine how stress and learning alter the survival of newly generated neurons in the female versus the male hippocampus. Recent studies from the host outgoing institution have shown that learning increased the survival of new neurons. However, exposure to uncontrollable stressful experience dramatically impairs learning in females. Therefore, we propose that uncontrollable but not controllable stress will reduce learning in females and prevent the increase in cell survival, whereas exposure to the stressful event will have no effect on cell survival in males. We further propose that these adverse effects in females can be prevented by chronic treatment with the common antidepressant fluoxetine. Finally, we will determine whether the presence of female sex hormones, estrogen and progesterone are necessary and will also correlate changes in neurogenesis with serotonergic activity/ 5-HT1A receptor expression in the hippocampus. The results from these experiments will provide critical information about how females respond to stress and hopefully will lead to new and improved treatment strategies for women suffering from depression. It is envisaged, that this project will permit the enhancement of the existing expertise, the researcher's transnational mobility and training and the establishment of international cooperation. Thus, it will contribute to European excellence and competitiveness.
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