Abstract
Hippocampal neurogenesis continues throughout the lifespan of adult mammals, but the rates decline dramatically with increasing age. Among the factors that have been shown to affect neurogenesis, aging has been shown to be one of its most potent regulators in mice. The mechanism for the decline in neurogenesis with age is thought to be related to age-dependent changes in local and systemic neuroendocrinology and neurochemistry, as well as internal changes to precursor cells that result in decreased reactivity to normal stimuli. Since most of the data about neurogenesis and age were established from rodent studies, we sought to study this relationship in nonhuman primates in five previously studied cohorts of bonnet monkeys (Macaca radiata). In the present study, we statistically analyze the relationship of age and hippocampal neurogenesis rates, as measured by the number of DCX expressing cells in the subgranular zone of the dentate gyrus in 71 subjects with ages ranging from 3.5 to 17 years. We observed a non-significant relationship between age and doublecortin for subjects less than nine years old (corresponding to young and full adulthood) but a linear significant decline for subjects 9 years or greater (middle age and senescence). In contrast to previous studies that show neurogenesis to decline linearly throughout the lifespan, this study shows that neurogenesis occurs steadily throughout adulthood and begins to decline in middle age in bonnet macaques.
Highlights
Neurogenesis, the birth of new neurons, occurs throughout adulthood in the dentate gyrus of the hippocampus [1]
We examined the means and standard deviations of the doublecortin staining rates for the five different studies that were used for the examination of the relationship between age and neurogenesis
On post-hoc Newman-Keuls analysis, it was revealed that the “ziprasidone” group exhibited neurogenesis rates that were significantly reduced in comparison to the “ECS” group and the “VFD1” group (p < 0.05)
Summary
Neurogenesis, the birth of new neurons, occurs throughout adulthood in the dentate gyrus of the hippocampus [1]. Newborn precursor cells arise from the subgranular zone of the dentate gyrus and, once having matured into granule cell neurons, and extend axonal projections along the mossy fiber tract to the CA3 region of the hippocampus, becoming integrated into the hippocampal circuitry [2,3,4,5]. There is a continuous decline in precursor cell proliferation and net hippocampal neurongenesis that occurs in rat [6] and mouse models [7]. In New World marmoset nonhuman primates, the number of bromodeoxyuridine (BrdU)-labeled cells in the dentate gyrus was shown to decline linearly with age [8]. In contrast to earlier experiments conducted in New World monkeys by other
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