Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11beta-hydroxysteroid dehydrogenase type 2.
Prenatal stress (PS) produces persistent abnormalities in anxiety-related behaviors, stress responsivity, susceptibility to psychopathology and hippocampal changes in adult offspring. The hippocampus shows a remarkable degree of structural plasticity, notably in response to stress and glucocorticoids. We hypothesized that PS would differentially affect hippocampal neurogenesis in rats selectively bred for genetic differences in anxiety-related behaviors and stress responsivity. Pregnant dams of high anxiety-related behavior (HAB) and low anxiety-related behavior (LAB) strains were stressed between days 5 and 20 of pregnancy. The survival of newly generated hippocampal cells was found to be significantly lower in 43-day-old HAB than in LAB male offspring of unstressed pregnancies. PS further reduced newly generated cell numbers only in HAB rats, and this was paralleled by a reduction in doublecortin-positive cell numbers, indicative of reduced neurogenesis. As maternal plasma corticosterone levels during PS were similar in both strains, we examined placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), which catalyses rapid inactivation of maternal corticosterone to inert 11-dehydrocorticosterone and thus serves as a physiological 'barrier' to maternal glucocorticoids. PS significantly increased placental 11beta-HSD2 activity in LAB, but not HAB, rats. We conclude that PS differentially affects the number of surviving newly generated cells and neurogenesis in HAB and LAB rats. The high sensitivity of hippocampal neurogenesis to PS in HAB rats is paralleled by a failure to increase placental 11beta-HSD2 activity after stress rather than by different maternal corticosterone responses. Hence, stress-induced placental 11beta-HSD2 expression may be critical in protecting the fetal brain from maternal stress-induced effects on adult neurogenesis.
Lucassen
P J
PJ
SILS-CNS, University of Amsterdam, Amsterdam, The Netherlands. lucassen@science.uva.nl
Bosch
O J
OJ
Jousma
E
E
Krömer
S A
SA
Andrew
R
R
Seckl
J R
JR
Neumann
I D
ID
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001008:Anxiety Disorders / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D002452:Cell Count; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D003345:Corticosterone / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009479:Neuropeptides / Q000032:analysis / Q000378:metabolism; D010920:Placenta / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology
C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003345:Corticosterone