Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible

TLDR

Acute stress is known to suppress hippocampal neurogenesis, but the long‑term effects of chronic stress on proliferation, apoptosis, and cell turnover in the rat dentate gyrus remain poorly understood. The study aimed to determine how three weeks of chronic unpredictable stress affect structural plasticity in the rat dentate gyrus, including proliferation, survival, apoptosis, volume, and cell number. Adult rats were exposed to chronic unpredictable stress for three weeks, after which proliferation, survival, apoptosis, volume, and cell counts were assessed via BrdU and Ki‑67 immunocytochemistry, and a separate cohort was allowed a three‑week recovery period to evaluate lasting effects. Both acute and chronic stress reduced cell proliferation, with acute effects reversing within 24 h and chronic effects partially recovering after three weeks yet remaining below controls, while apoptosis increased after acute stress but decreased after chronic stress, indicating that chronic stress suppresses both proliferation and apoptosis but most alterations normalize following recovery.

Abstract

Acute stress suppresses new cell birth in the hippocampus in several species. Relatively little is known, however, on how chronic stress affects the turnover, i.e. proliferation and apoptosis, of the rat dentate gyrus (DG) cells, and whether the stress effects are lasting. We investigated how 3 weeks of chronic unpredictable stress would influence the structural dynamic plasticity of the rat DG, and studied newborn cell proliferation, survival, apoptosis, volume and cell number in 10-week-old animals. To study lasting effects, another group of animals was allowed to recover for 3 weeks. Based on two independent parameters, bromodeoxyuridine (BrdU) and Ki-67 immunocytochemistry, our results show that both chronic and acute stress decrease new cell proliferation rate. The reduced proliferation after acute stress normalized within 24 h. Interestingly, chronically stressed animals showed recovery after 3 weeks, albeit with still fewer proliferating cells than controls. Apoptosis, by contrast, increased after acute but decreased after chronic stress. These results demonstrate that, although chronic stress suppresses proliferation and apoptosis, 3 weeks of recovery again normalized most of these alterations. This may have important implications for our understanding of the reversibility of stress-related hippocampal volume changes, such as occur, for example, in depression.