Effects of prenatal protein malnutrition and postnatal stress on the development of brainstem nuclei and the hippocampus in the rat

The present studies were undertaken to examine the effect of prenatal malnutrition on the pre- and postnatal generation of neurons in the rat. In the studies of prenatal neurogenesis, the effect of diet on the timing and the number of cells produced in the locus coeruleus (LC), dorsal raphe nucleus (DR), and median raphe nucleus (MR) was determined. In the studies of postnatal neurogenesis, the effects of diet and of acute stress on the number of granule cells generated in the fascia dentata were studied on postnatal (P) day 7 and 30. In a separate study, the effect of prenatal protein malnutrition on the germinal cell cycle of the fascia dentata granule cells was also examined on P7.; Bromodeoxyuridine (BrDU), which is incorporated into the DNA during the synthetic phase of the cell cycle, was used to determine the timing of neurogenesis in the brain stem nuclei, the number of postnatally generated cells in the fascia dentata, and the effect of stress on dentate granule cell production. Acute stress at P7 was induced by maternal separation and cooling, and on P30 by physical restraint. The length of the synthetic phase was determined with a single injection of [3H]-thymidine, another marker for cell division, followed by an additional injection of BrDU at various intervals.; The noradrenergic LC and serotonergic DR and MR were selected because of the involvement of their axonal projection in the early stages of cerebral cortical development. The postnatally generated cells of the fascia dentata were selected because their development is known to be altered by a variety of environmental conditions including malnutrition and stress. However, the combined effects of malnutrition and stress have not been previously explored. The only previous study of the effect of malnutrition on the cycle kinetics of the dentate granule cells was undertaken with a diet paradigm that spanned both pre- and postnatal periods; Both the timing and the number of neurons produced in the LC, DR, and MR were unaffected by prenatal malnutrition. In contrast, cell production in the fascia dentata of malnourished rats, when compared to controls, was significantly decreased on P7 and significantly increased on P30. Both P7 and P30 control rats showed a curtailment in cell production with acute stress, whereas the prenatally malnourished rats failed to show any significant effect of stress on cell production. Thus, the postnatal production of these short-axoned granule cells has been fundamentally altered by the diet as well as in their adaptation to acute stress. Finally, the effect of prenatal malnutrition on the cell cycle has been shown to be a significant prolongation in the synthetic phase.