Proliferation of granule cell precursors in the dentate gyrus of adult monkeys is diminished by stress

TLDR

Granule cell neurogenesis is established in adult rodents and tree shrews but has not yet been demonstrated in adult primates, and while BrdU labels proliferating cells, prior work indicates that stress can suppress precursor proliferation in these species. The study aimed to determine whether adult marmoset monkeys generate dentate gyrus neurons and whether acute stress alters precursor proliferation. Adult marmosets received BrdU injections and were perfused either 2 hr or 3 weeks later, and stressed animals were injected 1 hr after exposure to a resident‑intruder paradigm and perfused 2 hr later, with proliferating cells quantified and compared to unstressed controls. BrdU labeling revealed that adult marmosets generate granule neurons, with ~80 % of labeled cells expressing neuronal markers after 3 weeks, but a single stressful encounter markedly reduced the number of proliferating cells, indicating stress impairs precursor proliferation.

Abstract

Although granule cells continue to be added to the dentate gyrus of adult rats and tree shrews, this phenomenon has not been demonstrated in the dentate gyrus of adult primates. To determine whether neurons are produced in the dentate gyrus of adult primates, adult marmoset monkeys ( Callithrix jacchus ) were injected with BrdU and perfused 2 hr or 3 weeks later. BrdU is a thymidine analog that is incorporated into proliferating cells during S phase. A substantial number of cells in the dentate gyrus of adult monkeys incorporated BrdU and ≈80% of these cells had morphological characteristics of granule neurons and expressed a neuronal marker by the 3-week time point. Previous studies suggest that the proliferation of granule cell precursors in the adult dentate gyrus can be inhibited by stress in rats and tree shrews. To test whether an aversive experience has a similar effect on cell proliferation in the primate brain, adult marmoset monkeys were exposed to a resident-intruder model of stress. After 1 hr in this condition, the intruder monkeys were injected with BrdU and perfused 2 hr later. The number of proliferating cells in the dentate gyrus of the intruder monkeys was compared with that of unstressed control monkeys. We found that a single exposure to this stressful experience resulted in a significant reduction in the number of these proliferating cells. Our results suggest that neurons are produced in the dentate gyrus of adult monkeys and that the rate of precursor cell proliferation can be affected by a stressful experience.