Chronic stress: Implications for neuronal morphology, function and neurogenesis

Effect of chronic stress during adolescence in prefrontal cortex structure and function

“…Chronic stress also interferes with the function of the sympathetic nervous system and the HPA axis [10,14,52]. However, since several studies have demonstrated that animals adapt to the predictability of a single stressor agent [12,57], in our study we used different stressors in a non-predicable way [49,50,63].…”

“…Stress is the response of an organism to a threat, either explicit or not, which includes physiological or behavioral compensatory adaptations to maintain bodily homeostasis [8,9]. The body response to the stressor event proceeds through two distinct but interrelated phases, 1) a rapid fight or flight response due to sympathetic activation of the adrenal medula and the subsequent release of catecholamines in the bloodstream, and 2) a slow response that depends on the activation of the hypothalamicpituitary-adrenal axis, resulting on the release of glucocorticoids (cortisol in humans and corticosterone in other animals) by the adrenal cortex in the blood circulation [10][11][12][13][14][15].…”

Regulation of Structural Plasticity and Neurogenesis during Stress and Diabetes; Protective Effects of Glucocorticoid Receptor Antagonists

“…After the discovery that the hippocampal formation holds large numbers of GC receptors [3], a large body of evidence has been gathered, demonstrating that stress via elevated GC levels can affect both, hippocampal structure and function [4][5][6]. Cerebral impacts of GCs are considered to predominantly involve slow genomic actions following activation of mineralocorticoids (MRs) and GRs.…”

“…Short-term exposure to stressors induces behavioral adaptation and is considered harmless. Although prolonged GC (over)exposure is often thought to be associated with deleterious alterations in hippocampal excitability, long-term potentiation (LTP), and hippocampus-related memory performance, many positive effects of stress have been described as well, that depend on the type of stressor and its convergence in space and time [5,8,11].Prolonged exposure to stress may induce alterations in HPA feedback that can overexpose the brain and body to aberrant GC levels. Even though feedback is largely mediated through the GR, chronic stress may also alter the function of the MR that is implicated in tonic inhibitory control of the HPA axis and modulates AN [5,7].…”

“…Even higher doses are One concern is mifepristone's clinical efficacy, as highlighted by studies comparing treatment with mifepristone to placebo or other antidepressive and antipsychotic treatments (for a review see [62]). In a series of recent experimental studies [45,[63][64][65][66], mifepristone was also effective in rats that were exposed to 21 days of chronic multiple unpredictable stressors, a paradigm that altered many structural and functional parameters in the hippocampus (Figure 6.3•) [5,8]. Interestingly, treatment with a high dose of Q6 mifepristone during the final 4 days of this 21 day paradigm rapidly normalized the stress-induced reduction in adult generated cell numbers and neurogenesis in the hippocampal DG [45,66].…”