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Dynamics of hippocampal neurogenesis in adult humans.

ABSTRACT: Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived ¹?C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal neurons constituting one-third of the neurons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neurons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neurogenesis may contribute to human brain function.

SUBMITTER: Spalding KL

PROVIDER: S-EPMC4394608 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Dynamics of hippocampal neurogenesis in adult humans.

Spalding Kirsty L KL Bergmann Olaf O Alkass Kanar K Bernard Samuel S Salehpour Mehran M Huttner Hagen B HB Boström Emil E Westerlund Isabelle I Vial Celine C Buchholz Bruce A BA Possnert Göran G Mash Deborah C DC Druid Henrik H Frisén Jonas J

Cell 20130601 6

Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived ¹⁴C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal ...[more]

PMID: 23746839

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Project description:Comparison of neurodevelopmental sequences between species whose initial period of brain organization may vary from 100 days to 1,000 days, and whose progress is intrinsically non-linear presents large challenges in normalization. Comparing adult timelines when lifespans stretch from 1 year to 75 years, when underlying cellular mechanisms under scrutiny do not scale similarly, presents challenges to simple detection and comparison. The question of adult hippocampal neurogenesis has generated numerous controversies regarding its simple presence or absence in humans versus rodents, whether it is best described as the tail of a distribution centered on early neural development, or is several distinct processes. In addition, adult neurogenesis may have substantially changed in evolutionary time in different taxonomic groups. Here, we extend and adapt a model of the cross-species transformation of early neurodevelopmental events which presently reaches up to the equivalent of the third human postnatal year for 18 mammalian species (www.translatingtime.net) to address questions relevant to hippocampal neurogenesis, which permit extending the database to adolescence or perhaps to the whole lifespan. We acquired quantitative data delimiting the envelope of hippocampal neurogenesis from cell cycle markers (i.e., Ki67 and DCX) and RNA sequencing data for two primates (macaque and humans) and two rodents (rat and mouse). To improve species coverage in primates, we gathered the same data from marmosets (Callithrix jacchus), but additionally gathered data on a number of developmental milestones to find equivalent developmental time points between marmosets and other species. When all species are so modeled, and represented in a common time frame, the envelopes of hippocampal neurogenesis are essentially superimposable. Early developmental events involving the olfactory and limbic system start and conclude possibly slightly early in primates than rodents, and we find a comparable early conclusion of primate hippocampal neurogenesis (as assessed by the relative number of Ki67 cells) suggesting a plateau to low levels at approximately 2 years of age in humans. Marmosets show equivalent patterns within neurodevelopment, but unlike macaque and humans may have wholesale delay in the initiation of neurodevelopment processes previously observed in some precocial mammals such as the guinea pig and multiple large ungulates.

Dataset Information

Dynamics of hippocampal neurogenesis in adult humans.

Publications

Dynamics of hippocampal neurogenesis in adult humans.

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