The neurogenesis hypothesis of depression assumes that neurogenesis is influenced negatively by stressful experiences and positively by antidepressant treatment. Alterations in neurogenesis are believed

to play a decisive role in the pathology and treatment of major depression3,5; this view is supported by several converging lines of research. Neurodegeneration and neurogenesis Imaging and postmortem studies have demonstrated cellular loss in several brain areas, eg, in the prefrontal cortex and amygdala6-9 and in the paraventricular nucleus of the hypothalamus10 in depressed patients.10 High lacunar volume in white matter has been observed in Selleckchem GSK1120212 latelife mood disorders,11 as has reduced Inhibitors,research,lifescience,medical hippocampal volume.12,13 A negative correlation of the hippocampal volume and the length of the untreated depression, as

well as a normalization of the hippocampal volume in remission, have been demonstrated.13 Neurogenesis and cellular plasticity Adult neurogenesis was Inhibitors,research,lifescience,medical demonstrated in 1965 in rats and some years later in the human dentate gyrus of the hippocampus14 and in the subventricular zone of the lateral ventricle. It has been demonstrated that neurogenesis can be inhibited by physical and social stress, depression, and antidepressant treatment. Modulating factors seem to be novelty, fear, and learning.3 Possible mechanisms of action Inhibitors,research,lifescience,medical relating depression to a dysfunction in neurogenesis are psychological stress, glucose and insulin regulation, oxidative stress, a reduction in brain-derived neurotrophic factor (BDNF), and telomere shortening. Psychological stress and Inhibitors,research,lifescience,medical neuroinflammation Psychological stress and neuroinflammation lead to an activation of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis and proinflammatory cytokines are released. It has been proven Inhibitors,research,lifescience,medical that inflammatory cytokines can induce neurodegeneration in depression.15-18 For example, in 2009, Maes and colleagues concluded that chronic stress may exacerbate the release of proinflammatory cytokines and precipitate depressive episodes.15

The administration of high levels of proinflammatory cytokines can cause changes in behavior similar to depression, and the attenuation of an inflammatory response can reduce depressive symptoms.19-20 Glucose and insulin regulation Depression Bumetanide is often associated with higher levels of the stress-related hormone cortisol. In depressive patients suffering from hypercortisolemia, glucose and insulin regulation are abnormal. High levels of Cortisol have an anti-insulin effect. In a comprehensive review, Rasgon and colleagues21 have described how prolonged exposure to glucose intolerance and insulin resistance is associated with accelerated biological aging. Neurotoxic effects of hypercortisolemia have also been described.22 Oxidative stress Oxidative stress and inflammation are also called the “evil twins” of brain aging.