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% casein in diet) initiated at conception and imposed during the first 2 weeks of rat gestation on postnatal brain development. At the end of the malnutrition period, protein-restricted animals exhibited significantly smaller fetal body weight and brain cortical thickness than controls. At birth and thereafter, body weight was normalized in the progeny. Similarly, brain weight and cytoarchitecture were normal in postnatal animals. In contrast, we observed, during the first 2 postnatal weeks, several abnormalities of brain development which affected all the studied areas for most of the studied parameters: (i) delayed astrocytogenesis as shown by a reduced GFAP staining; (ii) delayed production of hyaluronan in the extracellular matrix studied with binding of biotinylated hyaluronectin; (iii) abnormal neuronal differentiation as shown by reduced expression of MAP-5 and increased expression of MAP-1; (iv) abnormal synaptogenesis as shown by the increased expression of synaptophysin in the basal ganglia; (v) decreased programmed cell death. In adult prenatally protein-restricted animals, all the above parameters were normalized excepted MAP-1 labeling which remained high. In addition, we observed slight alterations of the ventilatory response to hypoxia in adult animals. The present study demonstrates that early protein malnutrition during embryonic development induces multiple, transient alterations of brain development. However, the almost complete normalization in adults of brain architecture and differentiation as well as our physiological data strongly suggest a remarkable plasticity of the developing brain following an early aggression.
Gressens
P
P
Laboratoire de Neurobiologie et de Physiologie du Développement, INSERM CRI 96-03, Hôpital Robert-Debré, Paris, France. pierre.gressens@rdb.ap-hop-paris.fr
Muaku
S M
SM
Besse
L
L
Nsegbe
E
E
Gallego
J
J
Delpech
B
B
Gaultier
C
C
Evrard
P
P
Ketelslegers
J M
JM
Maiter
D
D
D000375:Aging / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000254:growth & development*; D053938:DNA Fragmentation; D018753:Diet, Protein-Restricted; D005260:Female; D005333:Fetus / Q000502:physiology*; D008297:Male; D009929:Organ Size; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011502:Protein-Energy Malnutrition / Q000196:embryology*; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration