Experience-Induced Neurogenesis in the Senescent Dentate Gyrus

TLDR

The study quantified neurogenesis in aged mice using confocal microscopy of BrdU‑labeled cells with neuronal and glial markers, followed by unbiased stereological counting. Neurogenesis persists in the dentate gyrus of senescent mice but declines with age, and environmental enrichment for 68 days markedly increases the survival of BrdU‑labeled neurons—tripling their number in 20‑month‑old mice and more than doubling it in 8‑month‑old mice—without affecting proliferation or glial cell numbers.

Abstract

We demonstrate here that under physiological conditions neurogenesis continues to occur in the dentate gyrus of senescent mice and can be stimulated by living in an enriched environment. Neurogenesis was investigated by confocal microscopy of three-channel immunofluorescent staining for the proliferation marker bromodeoxyuridine (BrdU) and neuronal and glial markers. Quantification was performed with unbiased stereological counting techniques. Neurogenesis decreased with increasing age. Stimulation of adult and aged mice by switching from standard housing to an enriched environment with opportunities for social interaction, exploration, and physical activity for 68 d resulted in an increased survival of labeled cells. Phenotypic analysis revealed that, in enriched living animals, relatively more cells differentiated into neurons, resulting in a threefold net increase of BrdU-labeled neurons in 20-month-old mice (105 vs 32 cells) and a more than twofold increase in 8-month-old mice (684 vs 285 cells) compared with littermates living under standard laboratory conditions. Corresponding absolute numbers of BrdU-positive astrocytes and BrdU-positive cells that did not show colabeling for neuronal or glial markers were not influenced. The effect on the relative distribution of phenotypes can be interpreted as a survival-promoting effect that is selective for neurons. Proliferation of progenitor cells appeared unaffected by environmental stimulation.