Neocortical neurogenesis in humans is restricted to development

Bhardwaj, Ratan D.; Curtis, Maurice A.; Spalding, Kirsty L.; Buchholz, Bruce A.; Fink, David; Björk‐Eriksson, Thomas; Nordborg, Claes; Gage, Fred H.; Druid, Henrik; Eriksson, Peter S.; Frisén, Jonas

doi:10.1073/pnas.0605177103

Cited by 403 publications

(309 citation statements)

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“…However, there are some published studies of human stem/progenitor cell fate that avoid recurrence to grafting to animal models. Through postmortem analyses of patients who had been treated with bromodeoxyuridine (BrdU) and neurosurgical resections, we have learned that new neurons are generated from dividing progenitor cells in the dentate gyrus, but not in the neocortex of the adult human brain [4][5][6]. Moreover, retrospective 14 C-dating can determine the average age of cells in postmortem samples of the human intestine, intercostal skeletal muscle, and brain, thus providing a new tool to measure cell turnover in human beings [4,7].…”

Section: Introductionmentioning

confidence: 99%

Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

Gago¹,

Pérez-López²,

Sanz-Jaka

et al. 2009

Stem Cells

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A major unanswered question in autologous cell therapy is the appropriate timing for cell isolation. Many of the putative target diseases arise with old age and previous evidence, mainly from animal models, suggests that the stem/progenitor cell pool decreases steadily with age. Studies with human cells have been generally hampered to date by poor sample availability. In recent years, several laboratories have reported on the existence, both in rodents and humans, of skin-derived precursor (SKP) cells with the capacity to generate neural and mesodermal progenies. This easily obtainable multipotent cell population has raised expectations for their potential use in cell therapy of neurodegeneration. However, we still lack a clear understanding of the spatiotemporal abundance and phenotype of human SKPs. Here we show an analysis of human SKP abundance and in vitro differentiation potential, by using SKPs isolated from four distinct anatomic sites (abdomen, breast, foreskin, and scalp) from 102 healthy subjects aged 8 months to 85 years. Human SKP abundance and differentiation potential decrease sharply with age, being extremely difficult to isolate, expand, and differentiate when obtained from the elderly. Our data suggest preserving human SKP cell banks early in life would be desirable for use in clinical protocols in the aging population.

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Section: Introductionmentioning

confidence: 99%

Age-Dependent Depletion of Human Skin-Derived Progenitor Cells

Gago¹,

Pérez-López²,

Sanz-Jaka

et al. 2009

Stem Cells

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show abstract

“…In other words, new neurons are relatively easy to detect in the numerous, homogeneous, densely packed populations of the olfactory bulb and dentate gyrus, while finding turnover in small, scattered neuronal populations requires much more sensitive detection methods. One recent study used a novel technique, radioactive carbon dating, to determine the average age of neurons dissociated from adult postmortem human cortex and found no evidence for neocortical adult neurogenesis (9). This method can reportedly detect adult birth in as few as 1% of analyzed cells (9), which should be sensitive enough to detect adult neurogenesis in the dentate gyrus or to detect neurogenesis occurring at a significant rate in cortical pyramidal neurons.…”

Section: Turnover Rate Is Similar In Neocortex and Dentate Gyrusmentioning

confidence: 99%

“…One recent study used a novel technique, radioactive carbon dating, to determine the average age of neurons dissociated from adult postmortem human cortex and found no evidence for neocortical adult neurogenesis (9). This method can reportedly detect adult birth in as few as 1% of analyzed cells (9), which should be sensitive enough to detect adult neurogenesis in the dentate gyrus or to detect neurogenesis occurring at a significant rate in cortical pyramidal neurons. However, turnover of a subclass of interneurons comprising 1% of the neuronal population would not be detectable with this method even if the entire population turned over continuously.…”

Section: Turnover Rate Is Similar In Neocortex and Dentate Gyrusmentioning

confidence: 99%

“…These early neocortical neurogenesis findings have been replicated in recent studies (3)(4)(5)(6)(7), but the existence of adult neurogenesis in the neocortex remains controversial, largely due to the existence of negative reports. In non-human primates, new neurons have been reported in prefrontal, inferior temporal, and posterior parietal cortex (3;6;7), though other groups have found no new neurons in the neocortex of adult primates, including humans (8)(9)(10)(11). In adult rodents, studies have reported finding new neurons in the anterior neocortex (5;7;12), but others found no new neocortical neurons in enriched, electroconvulsive seizure-treated, or control conditions (13; 14).…”

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confidence: 99%

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New Interneurons in the Adult Neocortex: Small, Sparse, but Significant?

Cameron

Dayer²

2008

Biological Psychiatry

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During the last decade, the intense study of adult hippocampal neurogenesis has led to several new lines of inquiry in the field of psychiatry. Although it is generally believed that adult mammalian neurogenesis is restricted to the hippocampus and olfactory bulb, a growing number of studies have described new neurons in the adult neocortex in both rodents and non-human primates. Interestingly, all of the new neurons observed in these studies have features of interneurons rather than pyramidal cells, the largest neuronal population of the neocortex. In this review, we discuss features of these interneurons that could help to explain why cortical neurogenesis has been so difficult to detect. In addition, these features suggest ways that production of even a small numbers of new neurons in the adult cortex could make a significant impact on neocortical function.It is widely accepted that adult neurogenesis occurs in two mammalian brain regions: the dentate gyrus and olfactory bulb. Interestingly, the earliest reports of adult neurogenesis in these two regions also described new neurons in the adult neocortex (1;2). These early neocortical neurogenesis findings have been replicated in recent studies (3-7), but the existence of adult neurogenesis in the neocortex remains controversial, largely due to the existence of negative reports. In non-human primates, new neurons have been reported in prefrontal, inferior temporal, and posterior parietal cortex (3;6;7), though other groups have found no new neurons in the neocortex of adult primates, including humans (8-11). In adult rodents, studies have reported finding new neurons in the anterior neocortex (5;7;12), but others found no new neocortical neurons in enriched, electroconvulsive seizure-treated, or control conditions (13; 14). Several additional studies have reported finding new neurons in the neocortex only after ischemia or targeted neuronal death (15-18). These contradictory findings are difficult to reconcile, because all of the studies of adult neurogenesis in the neocortex carried out within the past ten years have used essentially the same methods: injection and immunohistochemical detection of the S-phase marker bromodeoxyuridine (BrdU) to mark newly-born cells combined with immunohistochemistry for neuronal markers to determine whether the new cells are neurons. Virtually all positive and negative studies have used the neuron-specific marker NeuN (Neuronal Nuclei) to identify BrdU-labeled cells as mature neurons, and BrdUlabeled neurons in the adult rat neocortex have recently been characterized with several additional neuronal markers as well (5). The remainder of this review will describe features of new cortical neurons suggesting that they are interneurons rather than pyramidal neurons; Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review o...

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“…The generation of neocortical neurons is restricted to development and they are not exchanged in adulthood in healthy humans 1,2 . However, cortical ischemic stroke in animal models and humans has been suggested to induce both neurogenesis [3][4][5] and neuronal DNA rearrangements 6 , which could contribute to post-stroke recovery.…”

mentioning

confidence: 99%