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The Absence of Adult Human Hippocampal Neurogenesis Demonstrated in New Study

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Review of “Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults” from Nature by Stuart P. Atkinson

We currently accept that adult neurogenesis occurs in specific regions of the human hippocampus and while one study has numbered the production of new neurons in the hundreds per day [1], other studies suggest that this rate is much lower [2-4]. However, a new report from Jose Manuel Garcia-Verdugo (Universidad de Valencia, Spain), Zhengang Yang (Fudan University, Shanghai, China), and Arturo Alvarez-Buylla (University of California San Francisco, USA) disagrees. Writing in Nature, Sorrells et al. suggest that neurogenesis in the dentate gyrus of the human adult hippocampus is rare if it occurs at all [5]!

The authors assessed progenitor cells and young neuron number in post-mortem and post-operative human hippocampus samples that spanned human development. Their initial analyses in fetal and postnatal samples failed to detect a discrete layer of progenitors (the subgranular zone [SGZ]) as expected, and instead observed a sharp decline in the number of proliferating progenitors and young neurons within the dentate gyrus during development. Indeed, the study found very few young neurons in dentate gyrus samples from 7- to 13-year olds and no young neurons in adult samples. 

Interestingly, the authors did find evidence for SGZ formation and postnatal neurogenesis in macaques but noted the lack of hippocampal neurogenesis in large aquatic mammals known for large brains, longevity, and complex behavior [6], suggestive of inherent differences in adult neurogenesis across species.

Overall, this new study in this ever-evolving area has turned the field on its head by providing substantial evidence for a lack of neurogenesis in the dentate gyrus of the human hippocampus. However, in another twist to the story, a more recent Cell Stem Cell study supports the persistence of human hippocampal neurogenesis throughout the aging process [7].

The story of adult neurogenesis is turning epic in scale [8]; for all the new studies and the unexpected twists and turns in this area of research, stay tuned to the Stem Cells Portal.

References

  1. Spalding KL, Bergmann O, Alkass K, et al., Dynamics of hippocampal neurogenesis in adult humans. Cell 2013;153:1219-1227.
  2. Dennis CV, Suh LS, Rodriguez ML, et al., Human adult neurogenesis across the ages: An immunohistochemical study. Neuropathol Appl Neurobiol 2016;42:621-638.
  3. Eriksson PS, Perfilieva E, Bjork-Eriksson T, et al., Neurogenesis in the adult human hippocampus. Nat Med 1998;4:1313-7.
  4. Knoth R, Singec I, Ditter M, et al., Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS One 2010;5:e8809.
  5. Sorrells SF, Paredes MF, Cebrian-Silla A, et al., Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 2018;555:377.
  6. Patzke N, Spocter MA, Karlsson KAE, et al., In contrast to many other mammals, cetaceans have relatively small hippocampi that appear to lack adult neurogenesis. Brain Struct Funct 2015;220:361-83.
  7. Boldrini M, Fulmore CA, Tartt AN, et al., Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell;22:589-599.e5.
  8. Kempermann G, Gage FH, Aigner L, et al., Human Adult Neurogenesis: Evidence and Remaining Questions. Cell Stem Cell 2018.