Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation

By H. Georg, Kuhn, Heather, Dickinson-Anson, Fred, H. Gage. 1996

The hippocampus is one of the few areas of the rodent brain that continues to produce neurons postnatally. Neurogenesis reportedly persists in rats up to 11 months of age. Using bromodeoxyuridine (BrdU) labeling, the present study confirms that in the adult rat brain, neuronal progenitor cells divide at the border between the hilus and the granule cell layer (GCL). In adult rats, the progeny of these cells migrate into the GCL and express the neuronal markers NeuN and calbindin-D28k. However, neurogenesis was drastically reduced in aged rats. Six-to 27-month-old Fischer rats were injected intraperitoneally with BrdU to detect newborn cells in vivo and to follow their fate in the dentate gyrus. When killed 4–6 weeks after BrdU labeling, 12- to 27- month-old rats exhibited a significant decline in the density of BrdU- positive cells in the granule cell layer compared with 6-month-old controls. Decreased neurogenesis in aging rats was accompanied by reduced immunoreactivity for poly-sialylated neural cell adhesion molecule, a molecule that is involved in migration and process elongation of developing neurons. When animals were killed immediately (12 hr) after BrdU injection, significantly fewer labeled cells were observed in the GCL and adjacent subgranular zone of aged rats, indicative of a decrease in mitotic activity of neuronal precursor cells. The reduced proliferation was not attributable to a general aged- related metabolic impairment, because the density of BrdU-positive cells was not altered in other brain regions with known mitotic activity (e.g., hilus and lateral ventricle wall). The decline in neurogenesis that occurs throughout the lifespan of an animal can thus be related to a decreasing proliferation of granule cell precursors.

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Citations in the corpus

Neurogenesis in the Adult Hippocampus. (2015, background): “In the original publications on adult neurogenesis, the precursor cell population, from which neurogenesis originates, could be identified only through the detection of their proliferative activity and the absence of morphological characteristics of mature neurons and later neuron-specific antigens,”
The Adult Substantia Nigra Contains Progenitor Cells with Neurogenic Potential (2002, unknown): “Alvarez-Buylla, 1993; Luskin, 1993; Kuhn et al., 1996).”
Functional neurogenesis in the adult hippocampus (2002, methodology): “Criteria to include cells in the analysis were: (1) co-labelling with Alexa Fluor 594 (10 mg ml, Molecular Probes) or visual con®rmation of GFP in the pipette tip; (2) resting potential less than -50 mV; and (3) leak current less than 300 pA.”
Exercise Enhances Learning and Hippocampal Neurogenesis in Aged Mice (2005, methodology): “Immunohistochemistry for BrdU and immunofluorescent triple labeling for BrdU, neuronal nuclei (NeuN), and S100 were performed as described previously (Kuhn et al., 1996).”
Effects of voluntary exercise on synaptic plasticity and gene expression in the dentate gyrus of adult male Sprague-Dawley rats in vivo. (2004, methodology): “After a 10 day acclimation period to their respective housing conditions, animals were injected with BrdU (Sigma; 50 mg/kg i.p.; del Rio and Soriano, 1989; Kuhn et al., 1996) once daily for 5 consecutive days.”
Neural stem and progenitor cells in nestin‐GFP transgenic mice (2004, background): “3d), where neuronal progenitors reside (Kuhn et al., 1996; Gage, 2000).”
Biological underpinnings for lifelong learning machines (2022, background): “In adults, neurogenesis is known to occur in the dentate gyrus of the hippocampal formation 37 and in the subventricular zone of the lateral ventricles 38 .”
Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. (2003, background): “Apoptotic nuclei were seen in the GCL and hilus after irradiation but at much lower levels than in the SGZ .”
Transient expression of doublecortin during adult neurogenesis (2003, background): “The reduction of DCX-expressing cells in the dentate gyrus was consistent with the well documented age-dependent decrease in hippocampal neurogenesis (Seki and Arai, 1995; Kuhn et al., 1996; Kempermann et al., 1998).”
Computational influence of adult neurogenesis on memory encoding. (2009, unknown): “We measured the role of neurogenesis modulation by approximating two conditions that decrease neurogenesis levels: aging, which results in a chronic decrease in the number of new neurons (Kuhn et al., 1996), and stress, which can induce a rapid decrease in neurogenesis rates (Gould et al.”