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Neurogenesis in the dentate gyrus of the adult rat: Age-related decrease of neuronal progenitor proliferation
Author(s): Kuhn HG, DickinsonAnson H, Gage FH
Source: JOURNAL OF NEUROSCIENCE    Volume: 16    Issue: 6    Pages: 2027-2033    Published: MAR 15 1996  
Times Cited: 1,054     References: 41     
Abstract: 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-D-28k. 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 polysialylated 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 age-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.
Document Type: Article
Language: English
Addresses:
1. SALK INST, GENET LAB, SAN DIEGO, CA 92186 USA
Publisher: OXFORD UNIV PRESS INC, JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513
Subject Category: Neurosciences
IDS Number: TY536
ISSN: 0270-6474
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