NEUROGENESIS IN THE DENTATE GYRUS OF THE ADULT-RAT - AGE-RELATED DECREASE OF NEURONAL PROGENITOR PROLIFERATION

The hippocampus is one of the few areas of the rodent brain that conti nues to produce neurons postnatally. Neurogenesis reportedly persists in rats up to 11 months of age. Using bromodeoxyuridine (BrdU) labelin g, the present study confirms that in the adult rat brain, neuronal pr ogenitor cells divide at the border between the hilus and the granule cell layer (GCL). In adult rats, the progeny of these cells migrate in to 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 d etect newborn cells in vivo and to follow their fate in the dentate gy rus. When killed 4-6 weeks after BrdU labeling, 12- to 27-month-old ra ts exhibited a significant decline in the density of BrdU-positive cel ls in the granule cell layer compared with 6-month-old controls. Decre ased neurogenesis in aging rats was accompanied by reduced immunoreact ivity for polysialylated neural cell adhesion molecule, a molecule tha t is involved in migration and process elongation of developing neuron s. When animals were killed immediately (12 hr) after BrdU injection, significantly fewer labeled cells were observed in the GCL and adjacen t subgranular zone of aged rats, indicative of a decrease in mitotic a ctivity of neuronal precursor cells. The reduced proliferation was not attributable to a general age-related metabolic impairment, because t he density of BrdU-positive cells was not altered in other brain regio ns 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.