ReviewHippocampal Neurogenesis: Regulation by Stress and Antidepressants
Section snippets
Stress and Depression Affect the Hippocampus
The hippocampus has been firmly established to play a critical role in learning and memory. It also plays an important role in the brain’s response to psychosocial stress by regulating the release of hypothalamic corticotropin-releasing factor (CRF). Under stressful conditions, the paraventricular nucleus of the hypothalamus secretes CRF, which stimulates release of adrenocorticotropic hormone (ACTH) by the anterior pituitary. ACTH then stimulates release of glucocorticoids by the adrenal
Interaction of Stress Response and Monoamine Regulation in the Genetics of Major Depressive Disorder
Recent genetic studies suggest that the roles of stress and monoamines in MDD converge. Monoamine modulation has become the mainstay of antidepressant treatment. Inhibitors of the serotonin transporter are currently used for the treatment of all depressive and anxiety disorders. Genetic studies revealed a functional polymorphism resulting in transcriptional changes in the serotonin transporter gene (Lesch et al 1996). In a compelling study, Caspi and colleagues demonstrated that the
Psychosocial Stress and Monoamines Interact in Regulating Hippocampal Plasticity
Much of the evidence for convergence between stress and monoamines in animal models of depression comes from studies on the hippocampal response to stress and antidepressants. Chronic stress results in decreased transcription of the brain-derived neurotrophic factor (BDNF), whereas chronic treatment with monoamine modulators results in increased BDNF transcription. Both chronic stress and chronic treatment with monoamine modulators have opposing effects on two types of hippocampal plasticity.
Stress Hormones and Monoamines Regulate Adult Neurogenesis
Recent evidence indicates that psychosocial stress decreases neurogenesis via activation of the HPA axis and stimulation of the glucocorticoid receptor (GR). Salivary levels of cortisol are increased rapidly after exposure to psychosocial stress in humans (Kirschbaum et al 1996). Because both glucocorticoids (GC) and mineralocorticoids (MC) are produced by the adrenal glands, experimental adrenalectomy has been used extensively to study the importance of GC and MC in hippocampal response to
Animal Models of Depression
All of the experimental data on the role of neurogenesis in stress and antidepressant treatment come from analysis of brains from animals exposed to behavioral paradigms designed to model psychosocial stress and antidepressant response. Of course the subjective feeling of depressed mood is not possible to model in rodents. Therefore, different animal models of depression rely on reproducing either some aspect of behavioral manifestations of the depressive syndrome or a behavioral response to
Conclusions and Future Directions
This review focused on hippocampal plasticity following stress and reversal of these changes by treatment with modulators of monoamines. Clinical studies indicate that psychosocial stress management and monoamine regulation by pharmacologic agents are both important for improving depressive symptoms. Genetic studies suggest that stress and monoamines interact in depression (Caspi et al 2003) and its treatment (Binder et al 2004). Current pharmacologic treatments for major depression modulate
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