Impairment of neural precursor proliferation increases survival of cell progeny in the adult rat dentate gyrus

In the present study we show that a reduction in the number of neural precursor cells enhances survival of new granule cells in the dentate gyrus allowing the recovery of the proper granule cell layer structure. To diminish the number of newborn cells methylazoxymethanol (MAM), a toxic agent for proliferating cells, was injected during neonatal life. Proliferation of precursor cells and survival of newborn cells were assessed by BrdU administration to I-month-old rats when granule cell layer still shows a reduction in granule cell number in treated animals. Treatment with MAM reduced cell proliferation by 30%, and enhanced cell progeny survival: so that the final number of newborn cells exceeded control ones by 38%. Consistently, dentate granule cell death, assessed by the TUNEL method, was significantly decreased in the MAM rats. The enhanced survival of newborn granule cells and the consistent reduced cell death suggest a link between neurogenesis and regulation of granule cell number. A comparison with previous findings shows that the recovery in the long-term of granule cell layer may be due to the re-establishing of the progenitor pool size and/or to the rescue of cell progeny. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.