Unfortunately we have a very poor understanding of the retention of the effects of physical activity. Third,

we have a very poor understanding of the types of exercises that might be most useful to promote a healthier brain. It is conceivable that competitive sports like tennis offer additional benefits beyond noncompetitive sports because of their dependence on physical coordination, cognitive effort, and social interaction. In sum, although we have a solid understanding of the potential for physical activity to enhance cognitive and brain health in late life there remain many Tyrphostin AG-1478 in vivo unanswered questions for future research to pursue. Inhibitors,research,lifescience,medical Acknowledgments KIE was supported by the University of Pittsburgh Alzheimer’s Disease Research Center (P50 AG005133) and a research

grant from the National Inhibitors,research,lifescience,medical Institutes of Health (R01 DK095172). AGG was supported by National Institutes of Health grants R01 MH084921 and ACISR P30 MH090333. MAB was supported by the National Institutes of Health’s University of Pittsburgh Alzheimer’s Disease Research Center (P50 AG005133), ACISR P30 MH090333 and R01 MH080240.
Development of traditional pharmacological treatments for major depression has been based on the monoamine hypothesis of depression, inferring a depletion in the levels of serotonin, norepinephrine, and dopamine in the central nervous system as the underlying Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical pathophysiology of depression This hypothesis is supported by the mechanism of action of antidepressants, although the mechanism of action is not precisely understood and only about 50% of patients respond to antidepressants with this action.1 Thus, new types of antidepressants (eg, κ-receptor antagonists, melatonin receptor agonists, cytokines) Inhibitors,research,lifescience,medical are the subject of active research.1 The antidepressant effect of neuromodulation approaches (eg, vagus nerve stimulation therapy, deep brain

stimulation) have also challenged the monoamine hypothesis and favored the network hypothesis of depression. This Cell Metabolism hypothesis assumes that dysfunctions of large neuronal networks in the brain can be normalized through a modulation of one node of the respective network. In this article, we will rely on another explanatory approach to depression, namely on the neurogenesis hypothesis of depression.2 This hypothesis posits that changes in the rate of neurogenesis are the underlying mechanism in the pathology and treatment of major depression.3 We then discuss in what way depression according to the neurogenesis hypothesis can be used as model disease for cerebral aging, and possible implications for new treatment methods. Current knowledge on neurobiological effects of depression In current concepts, depression is seen as a chronic disease with recurrent episodes in the majority of cases.