Prenatal stress and neonatal rat brain development.
Chronic or repeated stress during human fetal brain development has been associated with various learning, behavioral, and/or mood disorders, including depression in later life. The mechanisms accounting for these effects of prenatal stress are not fully understood. The aim of this study was to investigate the effects of prenatal stress on early postnatal brain development, a disturbance of which may contribute to this increased vulnerability to psychopathology. We studied the effects of prenatal stress on fetal growth, stress-induced corticosterone secretion, brain cell proliferation, caspase-3-like activity and brain-derived neurotrophic factor protein content in newborn Fischer 344 rats. In addition to a slight reduction in birth weight, prenatal stress was associated with elevated corticosterone levels (33.8%) after 1 h of maternal deprivation on postnatal day 1, whereas by postnatal day 8 this pattern was reversed (-46.5%). Further, prenatal stress resulted in an approximately 50% decrease in brain cell proliferation just after birth in both genders with a concomitant increase in caspase-3-like activity within the hippocampus at postnatal day 1 (36.1%) and at postnatal day 5 (females only; 20.1%). Finally, brain-derived neurotrophic factor protein content was reduced in both the olfactory bulbs (-24.6%) and hippocampus (-28.2%) of prenatally stressed male offspring at postnatal days 1 and 5, respectively. These detrimental central changes observed may partly explain the increased susceptibility of prenatally stressed subjects to mood disorders including depression in later life.
Van den Hove
D L A
DL
Department of Pediatrics, Research Institute Growth and Development, Faculty of Medicine, Maastricht University, P. Debyelaan 25, P. O. Box 5800, 6202 AZ, Maastricht, The Netherlands. d.vandenhove@np.unimaas.nl
Steinbusch
H W M
HW
Scheepens
A
A
Van de Berg
W D J
WD
Kooiman
L A M
LA
Boosten
B J G
BJ
Prickaerts
J
J
Blanco
C E
CE
D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation; D003345:Corticosterone / Q000097:blood; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D011916:Rats, Inbred F344; D012149:Restraint, Physical / Q000009:adverse effects; D013315:Stress, Psychological / Q000503:physiopathology*
D019208:Brain-Derived Neurotrophic Factor; C505407:CASP3 protein, human; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; D003345:Corticosterone