Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: Implications for depression and antidepressant action☆

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

“…The most thoroughly documented stress-induced structural change is the dendritic reorganization that occurs parallel to the loss of spines and synapses and together with alterations in postsynaptic densities, suggesting general changes in neuronal connectivity. Chronic stress or experimentally increased corticosterone concentrations induce retraction of the apical dendrites of the CA3 and, to a lesser extent, of CA1 pyramidal cells and dentate granule cells [6,27,28]. Alterations in CA3 synapses and in the morphology of their mossy fiber terminals have also been described [27][28][29].…”

“…Electrophysiological, endocrinal, and behavioral data suggests that fast-acting corticosterone organizes the initial stage of the stress response through the MR [9]. Interestingly, there is also evidence for a fast-acting GR that requires endocannabinoids [10].The hippocampus is not only very sensitive to circulating GC levels, it is also important in emotional processing and key aspects of learning and memory, where adult neurogenesis (AN) has also been implicated [6,7]. Short-term exposure to stressors induces behavioral adaptation and is considered harmless.…”

“…Altered hippocampal function is likely to influence the activity of other brain structures, in particular, the prefrontal cortex and the amygdala which are key areas in emotional regulation and can, in turn, be influenced by these structures as well. Since the hippocampus indirectly provides negative feedback control of the HPA axis through a poorly understood trans-synaptic network [15], altered hippocampus function may contribute to HPA axis dysregulation, which is common in almost 50% of depressed patients [16].While depressive and related affective disorders are considered to have a neurochemical basis, recent studies suggest that impairments of structural plasticity, particularly when induced at an early age, contribute to the pathophysiology as well [6,[17][18][19]. In this review, we will focus on the hippocampal formation, because of the volume changes in depression [20] and the occurrence of AN in this structure.…”

“…Daughter cells of these progenitors proliferate at high frequency, often observed as bromodeoxyuridine (BrdU)-positive cell clusters and have been named amplifying neural progenitors • (Figure 6.2). As the newborn neurons mature, they Q5 extend axons and dendrites, followed by the formation of spines and functional synapses [6,38]. New neurons display characteristic functional properties such as lower threshold for induction of LTP and robust LTP [39].…”

“…Magnetic resonance imaging (MRI) and morphometric studies, for example, show that chronic psychosocial stressors result in a mild reduction in hippocampal volume, that is around 10% in tree shrews [20]. Effects of stress on hippocampal volume and hippocampal cell number are, however, relatively mild and subregion-specific and occur shortly after stressor onset, but prior to cognitive disturbances [6].The traditional explanation for this stress-induced hippocampal volume decrease was that elevated GCs in rodents have neurotoxic effects on the hippocampus. Neuronal death in the CA3 and CA1 subregions, in particular, was emphasized [23,24].…”