Chronic variable stress reduces the availability of neural precursors in the rat hippocampal dentate gyrus

TOSELLI A; RIVAROLA MA; POLLANO A; WILSON C; SUAREZ M; MIR F

Congreso; SAN 2023 Meeting; 2023

xposure to adverse life events can contribute to the development of depression. The dentate gyrus (DG) of the hippocampus, known for its remarkable plasticity through neurogenesis, is one of the regions sensitive to such alterations. Hypotheses like match/mismatch attempt to elucidate how the relationship between early-life experiences and later adulthood plays a crucial role in stress coping strategies. In this study, we aimed to investigate the impact of early maternal separation (SMT) and chronic variable stress (CVS), both individually and combined, on the neural precursor population. Male rats underwent 4.5 hours of SMT between postnatal days 1 to 21. Subsequently, between postnatal days 50 to 74, the rats were exposed to a CVS protocol and concurrently treated with either the antidepressant Tianeptine (TIA) at 10 mg/kg or vehicle. The number of neural precursors in the subgranular zone of the DG was quantified using immunohistochemistry targeting SOX2 and confocal microscopy. Our findings revealed that only CVS exposure led to a significant 46% reduction in the neural precursor cell population. Furthermore, this impact was morphologically distinct, with the supra-pyramidal zone being the most affected. Interestingly, TIA was effective in restoring the number of neural precursors to control levels only in the infrapyramidal zone. Collectively, our results cannot be explained by the match/mismatch hypothesis, suggesting that alternative hypotheses must be considered.