Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus
By Heather A. Cameron, R. McKay. The Journal of comparative neurology, 2001
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Knowing the rate of addition of new granule cells to the adult dentate gyrus is critical to understanding the function of adult neurogenesis. Despite the large number of studies of neurogenesis in the adult dentate gyrus, basic questions about the magnitude of this phenomenon have never been addressed. The S‐phase marker bromodeoxyuridine (BrdU) has been extensively used in recent studies of adult neurogenesis, but it has been carefully tested only in the embryonic brain. Here, we show that a high dose of BrdU (300 mg/kg) is a specific, quantitative, and nontoxic marker of dividing cells in the adult rat dentate gyrus, whereas lower doses label only a fraction of the S‐phase cells. By using this high dose of BrdU along with a second S‐phase marker, [3H]thymidine, we found that young adult rats have 9,400 dividing cells proliferating with a cell cycle time of 25 hours, which would generate 9,000 new cells each day, or more than 250,000 per month. Within 5–12 days of BrdU injection, a substantial pool of immature granule neurons, 50% of all BrdU‐labeled cells in the dentate gyrus, could be identified with neuron‐specific antibodies TuJ1 and TUC‐4. This number of new granule neurons generated each month is 6% of the total size of the granule cell population and 30–60% of the size of the afferent and efferent populations (West et al. [ 1991 ] Anat Rec 231:482–497; Mulders et al. [ 1997 ] J Comp Neurol 385:83–94). The large number of the adult‐generated granule cells supports the idea that these new neurons play an important role in hippocampal function. J. Comp. Neurol. 435:406–417, 2001. Published 2001 Wiley‐Liss, Inc.
Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience
View Paper: https://www.semanticscholar.org/paper/45c27c08fbb43f8728e69a7447366d4a4f74e088
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Citations in the corpus
- Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus (2004, background): “, thousands of new granule cells are produced per da”
- Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. (2008, background): “In the adult rat, 9000 new neurons are born per day and survive with a half-life of 28 days (Cameron and McKay, 2001).”
- The Adult Substantia Nigra Contains Progenitor Cells with Neurogenic Potential (2002, methodology): “However, in our paradigm we used BrdU at a concentration in the range of a dose that allowed the detection of a large pool of proliferating cells and their progeny in the adult hippocampus (Cameron and McKay, 2001), making it unlikely that any newly generated neurons were not labeled with BrdU.”
- How widespread is adult neurogenesis in mammals? (2007, result): “This study was a turning point in the field as it stimulated many investigations in experimental animals which produced further data regarding the neuronal identity of the new cell”
- Toll-like receptors modulate adult hippocampal neurogenesis (2007, result): “Similar results were obtained when we injected BrdU (200 mg kg −1 ) every 2 h for 16 h and excised the brains immediately after the last injectio”
- Adult hippocampal neurogenesis and its role in Alzheimer's disease (2011, background): “Young adult rats generate approximately 9,000 new cells in the SGZ each day, with a survival rate of ~50% [17].”
- Computational influence of adult neurogenesis on memory encoding. (2009, positive): “At the time of testing, the model GC layer grew at roughly 10% per month, similar to what has been estimated in young rats ($6%; Cameron and McKay, 2001).”
- Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood (2006, neutral): “dtd" [ ]> Neurogenesis in the hippocampus continues throughout adult lif”
- Cell Proliferation in Adult Hippocampus is Decreased by Inescapable Stress: Reversal by Fluoxetine Treatment (2003, neutral): “This 2-h time point was chosen because it represents one cell cycle of labeling (Cameron and McKay, 2001).”
- Anatomical gradients of adult neurogenesis and activity: young neurons in the ventral dentate gyrus are activated by water maze training (2009, positive): “To label adult-born DG granule cells, all rats were given two injections of 5- bromo-2 0 -deoxyuridine (BrdU; Sigma, 200 mg/kg/injection, dissolved at 20 mg/ml in saline, 0.007 N NaOH) spaced 10 h apart (Cameron and McKay, 2001; Snyder et al., 2005).”
- Spatial Learning Depends on Both the Addition and Removal of New Hippocampal Neurons (2007, background): “The dentate gyrus (DG) of the hippocampal formation is one of the few structures where adult neurogenesis occurs in mammals [4], and it has been estimated that several thousand new cells are generated daily [5,6].”
- Sparse activity of identified dentate granule cells during spatial exploration (2016, background): “%) of morphologically immature GCs relative to the total GC population in young adult rats (Cameron and McKay, 2001; Gould, 2006).”