MATERNAL PROTEIN RESTRICTION EARLY IN RAT PREGNANCY ALTERS BRAIN-DEVELOPMENT IN THE PROGENY

We assessed the effects of a dietary protein restriction (5% vs. 20% c asein in diet) initiated at conception and imposed during the first 2 weeks of rat gestation on postnatal brain development. At the end of t he malnutrition period, protein-restricted animals exhibited significa ntly smaller fetal body weight and brain cortical thickness than contr ols. At birth and thereafter, body weight was normalized in the progen y. Similarly, brain weight and cytoarchitecture were normal in postnat al animals. In contrast, we observed, during the first 2 postnatal wee ks, several abnormalities of brain development which affected all the studied areas for most of the studied parameters: (i) delayed astrocyt ogenesis as shown by a reduced GFAP staining; (ii) delayed production of hyaluronan in the extracellular matrix studied with binding of biot inylated hyaluronectin; (iii) abnormal neuronal differentiation as sho wn by reduced expression of MAP-5 and increased expression of MAP-1; ( iv) abnormal synaptogenesis as shown by the increased expression of sy naptophysin in the basal ganglia; (v) decreased programmed cell death. In adult prenatally protein-restricted animals, all the above paramet ers were normalized excepted MAP-1 labeling which remained high. In ad dition, we observed slight alterations of the ventilatory response to hypoxia in adult animals. The present study demonstrates that early pr otein malnutrition during embryonic development induces multiple, tran sient alterations of brain development. However, the almost complete n ormalization in adults of brain architecture and differentiation as we ll as our physiological data strongly suggest a remarkable plasticity of the developing brain following an early aggression. (C) 1997 Elsevi er Science B.V.