Adult-born neurons from the dorsal, intermediate, and ventral regions of the longitudinal axis of the hippocampus exhibit differential sensitivity to glucocorticoids

• Published in: Molecular psychiatry 2021-07, Vol.26 (7), p.3240-3252
• Main Authors: Levone, Brunno Rocha, Codagnone, Martin G., Moloney, Gerard M., Nolan, Yvonne M., Cryan, John F., O’ Leary, Olivia F.
• Format: Article
• Language: English
• Subjects: 13; 13/100; 13/106; 13/51; 14/63; 38; 631/378; 631/532; 82/51; Animals; Behavioral Sciences; Biological Psychology; Corticosteroids; Corticosterone; Dexamethasone; Glucocorticoids; Glucocorticoids - pharmacology; Health aspects; Hippocampus; Hippocampus (Brain); Hippocampus - metabolism; Medicine; Medicine & Public Health; Neural stem cells; Neurogenesis; Neurons; Neurons - metabolism; Neurosciences; Nuclear transport; Pharmacotherapy; Physiological aspects; Progenitor cells; Psychiatric research; Psychiatry; Rats; Receptors, Glucocorticoid - metabolism; Spatial discrimination learning; Spatial memory; Stress; Stress (Psychology)
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-020-0848-8

Hippocampal neurogenesis has been shown to play roles in learning, memory, and stress responses. These diverse roles may be related to a functional segregation of the hippocampus along its longitudinal axis. Indeed, the dorsal hippocampus (dHi) plays a predominant role in spatial learning and memory, while the ventral hippocampus (vHi) is predominantly involved in the regulation of anxiety, a behaviour impacted by stress. Recent studies suggest that the area between them, the intermediate hippocampus (iHi) may also be functionally independent. In parallel, it has been reported that chronic stress reduces neurogenesis preferentially in the vHi rather the dHi. We thus aimed to determine whether such stress-induced changes in neurogenesis could be related to differential intrinsic sensitivity of neural progenitor cells (NPCs) from the dHi, iHi, or vHi to the stress hormone, corticosterone, or the glucocorticoid receptor (GR) agonist, dexamethasone. Long-term exposure of rat NPCs to corticosterone or dexamethasone decreased neuronal differentiation in the vHi but not the dHi, while iHi cultures showed an intermediate response. A similar gradient-like response on neuronal differentiation and maturation was observed with dexamethasone treatment. This gradient-like effect was also observed on GR nuclear translocation in response to corticosterone or dexamethasone. Long-term exposure to corticosterone or dexamethasone treatment also tended to induce a greater downregulation of GR-associated genes in vHi-derived neurons compared to those from the dHi and iHi. These data suggest that increased intrinsic sensitivity of vHi NPC-derived neurons to chronic glucocorticoid exposure may underlie the increased vulnerability of the vHi to chronic stress-induced reductions in neurogenesis.