http://www.the-scientist.com/?articles.view/articleNo/35902/title/Human-Adult-NeurogenesisRevealed/
Human Adult Neurogenesis Revealed
Retrospective carbon dating of human hippocampal cells confirms
substantial adult neurogenesis and suggests that the process
contributes to brain function.
By Dan Cossins | June 7, 2013
CELL/SPALDING ET ALAbove-ground
nuclear
bomb tests carried out more than 50 years ago resulted in elevated
atmospheric levels of the radioactive carbon-14 isotope ( C), which steadily
declined over time. In a study published yesterday (June 7) in Cell,
researchers used measurements of C concentration in the DNA of brain cells
from deceased patients to determine the neurons’ age, and demonstrated
that there is substantial adult neurogenesis in the human hippocampus.
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“We provide thorough information on the extent of neurogenesis and we
show that there is surprisingly large amount,” said study author Jonas
Frisén of the Karolinksa Institute in Stockholm, Sweden.
“It’s a very impressive achievement,” said Gerd Kempermann of the German
Center for Neurodegenerative Diseases in Dresden, who was not involved
with the study. “It’s welcome to the field as a long-sought confirmation, but
it’s also more, because they model the dynamics” of adult neurogenesis and
propose a role for neural turnover in human cognition.
The first direct evidence for adult neurogenesis in humans came in 1998, but
the method used—injecting a chemical label that permanently integrates into
the DNA of dividing brain cells—is no longer available to researchers due to
safety concerns, so the results were never replicated. In addition, the
technique could not provide information on the number of new neurons
generated, so it was impossible to see if neurogenesis occurs in humans to
the same extent as in rodents, in which new neurons are known to influence
brain function.
To study neuronal turnover in humans, Frisén and colleagues developed a
strategy to retrospectively date cells in post mortem brains by measuring
the levels of C. Since C is taken up by plants, and by animals that eat
plants, humans also take up C at atmospheric levels—which have been
declining at a known rate since the Limited Test Ban Treaty of 1963 put an
end to above-surface nuclear bomb testing.
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The C finds its way into the DNA of proliferating cells, where it is integrated
into chromosomes as they are duplicated before division. The proportion
of C compared to the stable, and vastly more abundant, carbon-12 isotope
( C), the levels of which remain constant over time, provides a date of birth
for individual cells. “Basically, C provides a timestamp in every new-born
brain cell,” said Frisén, “and we have measured the age of brain cells by
reading that timestamp.”
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The researchers investigated the brains of 55 individuals of various ages,
from 19 to 92. Based on the ratio of C to C in DNA of neurons in the
dentate gyrus—a portion of the hippocampus known to be important for
learning and memory, where neurogenesis is thought to take place—the
team created a mathematical model to estimate the rate of turnover of
neurons. They calculated that one-third of the neurons in the hippocampus
are regularly renewed throughout life, amounting to the addition of roughly
1,400 new neurons per day, with the rate declining modestly with age.
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In the proposed model, a subpopulation of neurons continuously renews,
whereas another population does not renew at all. The renewing cells live for
a much shorter period of time than others, but are continuously turned over.
In mice, hippocampal neurons have enhanced synaptic plasticity for a limited
time after differentiation—meaning they more readily adapt the strength of
connections in response to new stimuli. “These [young cells] are required for
separating similar experiences as distinct memories,” said Frisén. “For us
that means telling apart the Beatles and the Rolling Stones, rather than
lumping the two together as rock and roll music.”
If new neurons are also more plastic in humans, he suggests, neurogenesis
may play a key role in brain function by maintaining a steady supply of
younger cells—even though there is an overall loss of hippocampal neurons
as we age.
“By staying ‘forever young,’ the dentate gyrus could command unique
solutions to computational problems only found in the brain region central to
learning, memory, and many higher cognitive functions considered essential
for humans,” wrote Kempermann in a perspective on the paper in Science.
Moreover, there is evidence from animal models that reduced neurogenesis
is implicated in psychiatric disease, leading Frisén and colleagues to suggest
that young neurons in the dentate gyrus may also play a key role in mood
regulation. “What we want to do next is to look back at medical history of
these [and other] subjects . . . to see if depression or other psychiatric
conditions appear to be related to neurogenesis,” he said.
K.L Spalding et al., “Dynamics of hippocampal neurogenesis in adult
humans,” Cell, 153:1219-27, 2013.
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Volume 153, Issue 6, p1219–1227, 6 June 2013
Article
Switch to Standard View
Dynamics of Hippocampal Neurogenesis in Adult Humans
Kirsty L. Spalding8
,
Olaf Bergmann8
,
Kanar Alkass
,
Samuel Bernard
,
Mehran Salehpour
,
Hagen B. Huttner
,
Emil Boström
,
Isabelle Westerlund
,
Céline Vial
,
Bruce A. Buchholz
,
Göran Possnert
,
Deborah C. Mash
,
Henrik Druid
,
Jonas Frisén
These authors contributed equally to this work
8
Open Archive
DOI: http://dx.doi.org/10.1016/j.cell.2013.05.002
|
Highlights

•Nuclear-bomb-test-derived
neurogenesis
C in human hippocampal neurons reveals adult
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
•One-third of hippocampal neurons are subject to exchange

•The annual turnover rate is 1.75% within the renewing fraction in adult humans

•The extent of adult neurogenesis is comparable in middle-aged humans and
mice
Summary
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 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.
Received: March 11, 2013; Received in revised form: April 25, 2013; Accepted: April 29, 2013;
© 2013 Elsevier Inc. Published by Elsevier Inc.