Dynamics of Hippocampal Neurogenesis in Adult Humans

Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
Cell (Impact Factor: 32.24). 06/2013; 153(6):1219-27. DOI: 10.1016/j.cell.2013.05.002
Source: PubMed


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 (14)C 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.

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    • "Several decades have passed since Altman and Das [1] suggested that the mammalian adult brain is able to generate new neurons. Today, it is well-established that the adult brain of humans and other mammals generates new neurons throughout life [1] [2] [3] [4] [5]. The new neurons are produced in discrete regions of the adult brain under normal conditions, the subgranular zone (SGZ) of the dentate gyrus (DG) of the hippocampus, where new granule cells are generated, and subventricular zone (SVZ) of the lateral ventricle, where newly generated neurons then migrate through the rostral migratory stream (RMS) to the olfactory bulb to become interneurons [6]. "
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    ABSTRACT: The adult brain of humans and other mammals continuously generates new neurons throughout life. However, this neurogenic capacity is limited to two brain areas, the dentate gyrus (DG) of the hippocampus and the subventricular zone (SVZ) of the lateral ventricle. Although the DG generates new neurons, its neurogenic capacity declines with age and neurodegenerative diseases such as Alzheimer's disease (AD) and Huntington's disease (HD). This review focuses on the role of newly-born neurons in cognitive processes, and discusses some of the strategies proposed in humans and animals to enhance neurogenesis and counteract age-related cognitive deficits, such as physical exercise and intake of natural products like omega-3 fatty acids, curcumin andflavanols.
    Current topics in medicinal chemistry 06/2015; 15(21). DOI:10.2174/1568026615666150610141524 · 3.40 Impact Factor
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    • "Accelerator Mass Spectrometry (AMS) was performed as described previously (Spalding et al., 2013). Purified DNA samples as described above were lyophilized to dryness. "
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    ABSTRACT: The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell 06/2015; 161(7). DOI:10.1016/j.cell.2015.05.026 · 32.24 Impact Factor
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    • "However, in humans, a recent study measuring 14 C concentration in neuronal nuclei found a high turnover rate in the human hippocampus, 700 new neurons are added in each side per day, corresponding to an annual turnover of 1.75% of the neurons. These rates are comparable in middle-aged human and mice, suggesting adult hippocampal neurogenesis plays an important role in the maintenance of brain function (Spalding et al., 2013). SVZ mainly provides GABAergic granule and periglomerular new interneurons to the OB. "
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    ABSTRACT: New neurons are continually generated in the subependymal layer of the lateral ventricles and the subgranular zone of dentate gyrus during adulthood. In the subventricular zone, neuroblasts migrate a long distance to the olfactory bulb where they differentiate into granule or periglomerular interneurons. In the hippocampus, neuroblasts migrate a short distance from the subgranular zone to the granule cell layer of the dentate gyrus to become granule neurons. In addition to the short-distance inputs, bulbar interneurons receive long-distance centrifugal afferents from olfactory-recipient structures. Similarly, dentate granule cells receive differential inputs from the medial and lateral entorhinal cortices through the perforant pathway. Little is known concerning these new inputs on the adult-born cells. In this work, we have characterized afferent inputs to 21-day old newly-born neurons. Mice were intraperitoneally injected with bromodeoxyuridine. Two weeks later, rhodamine-labeled dextran-amine was injected into the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral and medial entorhinal cortices. One week later, animals were perfused and immunofluorescences were carried out. The data show that projection neurons from the mentioned structures, establish putative synaptic contacts onto 21-day-old neurons in the olfactory bulb and dentate gyrus, in some cases even before they start to express specific subpopulation proteins. Long-distance afferents reach middle and outer one-third portions of the molecular layer of the dentate gyrus and granule and, interestingly, periglomerular layers of the olfactory bulb. In the olfactory bulb, these fibers appear to establish presumptive axo-somatic contacts onto newly-born granule and periglomerular cells.
    Frontiers in Neuroanatomy 02/2015; 9:4. DOI:10.3389/fnana.2015.00004 · 3.54 Impact Factor
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