Editors' ChoiceNEUROGENESIS

Adult neurogenesis in humans: Dogma overturned, again and again?

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Science Translational Medicine  11 Apr 2018:
Vol. 10, Issue 436, eaat3893
DOI: 10.1126/scitranslmed.aat3893

Abstract

The controversy continues as to whether new neurons are born in adult human hippocampus.

For most of the twentieth century, there was a general consensus that brain cells could not renew themselves once the developmental period was over. Then, especially over the last two decades, overwhelming evidence gradually accumulated for the capacity of new neurons to be born in the adult brain in two clearly defined locations: the subventricular zone and the dentate gyrus (DG) of the hippocampus. The hippocampus is well known to play important roles in learning and memory, and this adult DG neurogenesis has not only been implicated in memory but has led to ideas that it could be harnessed to treat neurodegenerative and neuropsychiatric disorders. However, while the story is clear in rodents, whether and to what extent adult neurogenesis occurs in humans has remained controversial.

Now, the near-simultaneous publication of two papers with opposing messages fuels this controversy and animates the debate. Sorrells et al. report that humans uniquely appear to lack adult DG neurogenesis. They conducted a careful immunohistochemical study of hippocampal DG in 59 human subjects, and, using a series of well-known markers for neural progenitors and immature neurons, they hunted for evidence of newborn DG neurons in brain tissue ranging from 14 gestational weeks to 77 years old. Neurogenesis, robust in embryos, rapidly decreased with advancing age, with none seen in samples from individuals older than 13 years. Conversely, Boldrini et al. find that hippocampal neurogenesis not only occurs in adult humans but does not appear to decline with aging. Although the two studies used very similar immunohistochemical approaches, including many of the same markers, the study by Boldrini et al. only examined ages from 14 to 79 years, a time frame during which Sorrells et al. saw no dramatic changes. It is hard to directly compare the absolute numbers of newborn neurons reported by the two studies, as Boldrini et al. use a stereology approach to extrapolate total cell numbers across entire DG regions. However, they may not be so different: a few thousand cells in the whole anterior DG is arguably still relatively rare. Perhaps the question should be: how rare is rare? And are rare newborn hippocampal neurons enough to impact learning, mood, and even brain repair? Further studies are clearly needed. What still seems likely is that if neurons are born in human adulthood, they may be relatively few and far between. Adult neurogenesis declines with age in most species examined (and fascinatingly, may be absent in whales and dolphins, also notable for longevity and good memories), so perhaps we should be focusing more on neurogenesis occurring in childhood/adolescence, trying to understand whether this period can be extended and whether juvenile newborn cells can help treat neurological disorders.

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