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

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 Ϸ80% 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.

A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression

“…The hippocampi of depressed patients are significantly smaller than those of healthy individuals (Sheline, 2000). This reduced volume may be the result of decreased neurogenesis in depressed individuals, a possi-bility supported by the findings that hippocampal neurogenesis is reduced by stress (Gould et al, 1998) and increased by antidepressant treatment (Malberg et al, 2000). The parallel changes in BDNF levels and neurogenesis in response to stress and antidepressant treatment suggest a connection between BDNF and hippocampal neurogenesis.…”

Regulation of Adult Neurogenesis by Antidepressant Treatment

“…Gould and McEwen have reported that exposure of marmoset monkeys or tree shrews to intruder stress for only a short period of time (1 h) down-regulates the rate of neurogenesis in adult hippocampus see Gould et al (1998). Administration of adrenal-glucocorticoids also decreases neurogenesis in adult hippocampus see McEwen1999), indicating that activation of the HPA axis and release of glucocorticoids underlies the downregulation of neurogenesis in response to stress.…”

“…The emphasis on studies of hippocampus stems in part from the work of McEwen and colleagues demonstrating that stress can have profound effects on the morphology of hippocampal neurons (see McEwen 1999;Gould et al 1998). This includes a decrease in the dendritic arborization of CA3 pyramidal neurons and down-regulation of neurogenesis of granule cells in adult dentate gyrus.…”

Changes of cell proliferation and differentiation in the developing brain of mouse

“…However, only recently has neurogenesis become accepted as a general phenomenon in the brains of birds [1] , rodents [2][3][4][5] , monkeys [6] , and humans [7] . Further studies demonstrated that neurogenesis persisted in the mammal forebrain throughout the whole life [8,9] , and was modulated by both physiological stimuli and pathophysiological conditions [10,11] .…”