Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice

TLDR

Adult hippocampal neurogenesis is ongoing, yet it is unclear whether new neurons persist long‑term or are transient. Researchers labeled dividing hippocampal cells with BrdU and tracked them over 1 day to 11 months using immunofluorescence and confocal microscopy. BrdU‑labeled neurons remained stable in number and position for at least 11 months, indicating that adult neurogenesis produces lasting neurons whose final number and localization are set early; immature markers peaked early and vanished after 4 weeks, and no mature markers were detected in early BrdU/nestin‑positive cells.

Abstract

New neurons are continually generated in the adult hippocampus, but the important question, whether adult neurogenesis is transient or leads to the lasting presence of new neurons, has not yet been answered. Dividing cells were labeled with bromodeoxyuridine (BrdU) and were investigated by means of immunofluorescence and confocal microscopy at several time-points 1 day to 11 months thereafter. BrdU-labeled neurons remained stable in number and in their relative position in the granule cell layer over at least 11 months. This finding implies that the addition of new neurons is not transient and that their final number and localization are determined early. By contrast, expression of immature markers beta-III-tubulin and doublecortin in BrdU-labeled cells, peaked early after division and was not detectable after 4 weeks. In transgenic mice expressing enhanced green fluorescent protein under the nestin promoter none of the BrdU/nestin-positive cells early after division expressed the mature marker NeuN, confirming that no dividing neurons were detected. These new data suggest that new neurons are recruited early from the pool of proliferating progenitor cells and lead to a lasting effect of adult neurogenesis.