Progesterone Promotes the Survival of Newborn Neurons in the Dentate Gyrus of Adult Male Mice

This study found that progesterone (P4) significantly increased the survival of newborn neurons in the hippocampal dentate gyrus of adult male mice, particularly when administered shortly after neuron production. P4 doubled the number of 28- and 56-day-old neurons compared to controls, without affecting the number of very young neurons. The effect was specific to P4, as other hormones like androstenedione, testosterone, and estradiol did not replicate it, and it was not due to P4 metabolites. The P4 receptor antagonist RU486 partially suppressed the effect, while inhibitors of Src, MEK, or PI3K completely suppressed it, indicating that P4's action involved these pathways. Additionally, P4 treatment improved spatial learning and memory, suggesting a link between enhanced neuron survival and cognitive function.