Adult Neurogenesis in Humans

Abstract

Adult neurogenesis appears very well conserved among mammals. It was, however, not until recently that quantitative data on the extent of this process became available in humans, largely because of methodological challenges to study this process in man. There is substantial hippocampal neurogenesis in adult humans, but humans appear unique among mammals in that there is no detectable olfactory bulb neurogenesis but continuous addition of new neurons in the striatum.

Figure 1.

Retrospective birth dating of cells. Schematic depiction of the strategy to retrospectively birth date cells. Nuclear bomb tests during the Cold War resulted in a large addition of ¹⁴C to the atmosphere. ¹⁴C in the atmosphere reacts with oxygen to form ¹⁴CO₂, which is taken up by plants in photosynthesis. Eating plants or animals living off plants results in the atmospheric ¹⁴C concentrations at any given time being mirrored in the human body. When a cell divides and duplicates its genome, it will integrate ¹⁴C in DNA with a concentration corresponding to that in the atmosphere at any given time. Measuring the ¹⁴C concentration in genomic DNA allows determination of when cells were born.

Figure 2.

Neuronal turnover in the adult human hippocampus. (A) Schematic illustration of the representation of measured ¹⁴C concentrations in genomic DNA based on the year of birth for individuals born before (orange circle) or after (red circle) the nuclear bomb tests. The black line indicates the ¹⁴C concentration in the atmosphere at different time points in the last century. (B) Individually measured ¹⁴C concentrations in genomic DNA of human hippocampal neurons.¹⁴C concentrations above the atmospheric ¹⁴C curve, for subjects born before the onset of nuclear bomb tests, and data points below the curve, for subjects born after the nuclear tests, indicate cell turnover. (C) Individual turnover rates for neurons within the renewing fraction were computed based on individual data fitting (data from Spalding et al. 2013). The number of doublecortin (DCX)-positive cells per mm² in the dentate gyrus (data from Knoth et al. 2010) shows a similar modest decline during adult ages as the computed neuronal turnover rates. Straight lines depict linear regression curves, with the regression line for DCX cell counts calculated for individuals 10 years and older. Individual turnover rate calculations are sensitive to deviations in measured ¹⁴C, and values <0.001 or >1.5 were excluded from the plot; however, the full dataset is given in Spalding et al. (2013).

Figure 3.

Dynamics of hippocampal neurogenesis in humans. Schematic representation of the change in neuronal number and turnover in the human hippocampus. The dentate gyrus neurons constitute the population above the white line, and the other subdivisions of the hippocampus are shown below the white line. Neurons generated before birth of the individual are depicted in black, and decade cohorts of new neurons are shown in shades of gray. The proportion of cells shown in light gray represent the neurons generated during the last decade, the next shade darker represent the neurons generated the decade before that and so on. Newborn neurons have specific functional properties, and the neurons generated during the last year are depicted in gold. (Figure adapted from Spalding et al. 2013; reproduced, with permission, from the author.)

Figure 4.

Interspecies comparison of the extent of adult hippocampal neurogenesis. Representation of the proportion of newborn neurons to old neurons in the dentate gyrus, based on published data (Kempermann et al. 1997; Kornack and Rakic 1999; Jabès et al. 2010; Spalding et al. 2013). The extent of neurogenesis in 1-year-old mice was estimated from data from the 2-month-old mouse and the reduction in hippocampal neurogenesis with age in mice (Ben Abdallah et al. 2010).