Glucocorticoid ‐mediated mechanisms of hippocampal damage: contribution of subgranular neurogenesis

AbstractA  comprehensive overview of the interplay between glucocorticoids (GCs) and adult hippocampal neurogenesis (AHN) is presented, particularly, in the context of a diseased brain. The effectors of GCs in the dentate gyrus neurogenic niche of the hippocampal are reviewed, and the consequences of the G C signaling on the generation and integration of new neurons are discussed. Recent findings demonstrating how GC signaling mediates impairments of the AHN in various brain pathologies are overviewed. GC‐mediated effects on the generation and integration of adult‐born neurons in the hippocampal d entate gyrus depend on the nature, severity, and duration of the acting stress factor. GCs realize their effects on the AHN primarily via specific glucocorticoid and mineralocorticoid receptors. Disruption of the reciprocal regulation between the hypothalamic–pituitary–adrenal (HPA) axis and the generation of the adult‐born granular neurons is currently considered to be a key mechanism implicating the AHN into the pathogenesis of numerous brain diseases, including those without a direct hippocampal damage. These alterations vary from reduced proliferation of stem and progenitor cells to increased cell death and abnormalities in morphology, connectivity, and localization of young neurons. Although the involvement of the mutual regulation between the HPA axis and the AHN in the pathogenesis of cognitive deficits and mood impairments is evident, several unresolved critical...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: REVIEW Source Type: research