Postnatal development of rat dentate gyrus: effects of methylazoxymethanol administration.

In order to investigate the role of postnatal neurogenesis in granule cell number control in the rat dentate gyrus, we administered Methylazoxymethanol (MAM), a drug able to prevent cells from dividing, on P3, P5, P7, P9, when the most granule cells are produced. The effect of MAM on the number of proliferating precursors and of granule cells was examined at P16 and P90. We used 5-bromo-2'-deoxyuridine administration to label proliferating cells and immunohistochemistry to characterize the cell phenotype using neuron markers TUC 4, PSA-NCAM, Calbindin D28K and glial marker GFAP. At 16 days of age in MAM-treated rats we observed a significant decrease of BrdU-positive cells. Consistently, a decrease in density and number of granule cells was found compared to the controls. At 90 days the dentate gyrus of treated rats showed a complete recovery: no differences in the density, total number of neurons, the BrdU- and TUC 4-positive cells were revealed with respect to the controls. No deficits were evident in performance on the water maze in MAM-treated rats. These data suggest that the dentate gyrus is able to re-establish the proliferative zone and to rebuild the granule cell layer following neonatal MAM administration.