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18 Regulation of Hippocampal Neurogenesis by Systemic Factors Including Stress, Glucocorticoids, Sleep, and Inflammation

Paul J. Lucassen, Charlotte A. Oomen, Anne-Marie van Dam, Boldizsár Czéh


This chapter summarizes and discusses the regulation of adult neurogenesis and hippocampal cellular plasticity by systemic factors. We focus on the role of stress, glucocorticoids, and related factors such as sleep deprivation and inflammation.

Ever present as stress may be in the modern Western society, it represents an old, yet essential, alarm system for an organism. By definition, stress systems are activated whenever a discrepancy occurs between an organism’s expectations and the reality it encounters, particularly when it involves a threat to the organism’s homeostasis, well-being, or health.

Lack of information, loss of control, unpredictability, and uncertainty when faced with predator threat in animals or psychosocial demands in humans can all produce stress signals. The same holds for perturbations of a physical or biological nature, such as food shortage, injury, or inflammation. Various sensory and cognitive signals converge to activate a stress response that triggers several adaptive processes in the body and brain aimed to restore homeostasis.

In mammals, the stress response develops in a stereotypic manner through three phases: (1) an initial alarm reaction, (2) resistance, and, only after prolonged exposure, (3) exhaustion. The first phase largely involves activation of the sympathoadrenal system through the rapid release of epinephrine and norepinephrine from the adrenal medulla; these hormones elevate basal metabolic rate and increase blood flow to vital organs such as the heart and muscles.

At a later stage, the limbic hypothalamus-pituitary-adrenal (HPA) system is activated, i.e., a classic neuroendocrine circuit in which...

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