Prolactin prevents chronic stress-induced decrease of adult hippocampal neurogenesis and promotes neuronal fate

Chronic exposure to stress results in a reduction of hippocampal neurogenesis and of hippocampal volume. We examined whether prolactin (PRL), a regulator of the stress response and stimulator of neurogenesis in the subventricular zone, influences neurogenesis in the hippocampal dentate gyrus (DG) of chronically stressed adult C57BL/6 male mice. Chronically stressed (4 h daily immobilization for 21 d) or nonstressed mice were treated with either ovine PRL or vehicle between days 1-14. BrdU was injected daily between days 1-7 to evaluate cell survival and fate, or twice on day 21 to evaluate cell proliferation. Hippocampal cell proliferation was unchanged by either stress exposure or PRL at the end of the treatments. In contrast, the number of cells in the DG that incorporated BrdU during the first phase of the experiment and survived to the end of the experiment was decreased in vehicle-treated stressed mice compared with PRL- or vehicle-treated nonstressed control mice. Stressed animals receiving PRL had significantly more BrdU-labeled cells than vehicle-treated stressed mice at this time point. Cell fate analysis revealed a higher percentage of neurons in PRL- compared with vehicle-treated stressed mice. The results demonstrate that PRL protects neurogenesis in the DG of chronically stressed mice and promotes neuronal fate.