Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11 beta-hydroxysteroid dehydrogenase type 2

P. J. Lucassen; O. J. Bosch; E. Jousma; S. A. Kroemer; R. Andrew; J. R. Seckl; I. D. Neumann

doi:10.1111/j.1460-9568.2008.06543.x

Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11 beta-hydroxysteroid dehydrogenase type 2

P. J. Lucassen, O. J. Bosch, E. Jousma, S. A. Kroemer, R. Andrew, J. R. Seckl, I. D. Neumann

Research output: Contribution to journal › Article › peer-review

Abstract

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 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-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 11 beta-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 11 beta-HSD2 activity after stress rather than by different maternal corticosterone responses. Hence, stress-induced placental 11 beta-HSD2 expression may be critical in protecting the fetal brain from maternal stress-induced effects on adult neurogenesis.

Original language	English
Pages (from-to)	97-103
Number of pages	7
Journal	European Journal of Neuroscience
Volume	29
Issue number	1
DOIs	https://doi.org/10.1111/j.1460-9568.2008.06543.x
Publication status	Published - Jan 2009

Keywords / Materials (for Non-textual outputs)

depression
doublecortin
early life
hippocampus
HPA axis

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10.1111/j.1460-9568.2008.06543.x

http://onlinelibrary.wiley.com/doi/10.1111/j.1460-9568.2008.06543.x/abstract

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Lucassen, P. J., Bosch, O. J., Jousma, E., Kroemer, S. A., Andrew, R., Seckl, J. R., & Neumann, I. D. (2009). Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11 beta-hydroxysteroid dehydrogenase type 2. European Journal of Neuroscience, 29(1), 97-103. https://doi.org/10.1111/j.1460-9568.2008.06543.x

@article{a3d33948521f40ebb599423ce54c47d5,

title = "Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11 beta-hydroxysteroid dehydrogenase type 2",

abstract = "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 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-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 11 beta-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 11 beta-HSD2 activity after stress rather than by different maternal corticosterone responses. Hence, stress-induced placental 11 beta-HSD2 expression may be critical in protecting the fetal brain from maternal stress-induced effects on adult neurogenesis.",

keywords = "depression , doublecortin , early life , hippocampus , HPA axis",

author = "Lucassen, {P. J.} and Bosch, {O. J.} and E. Jousma and Kroemer, {S. A.} and R. Andrew and Seckl, {J. R.} and Neumann, {I. D.}",

year = "2009",

month = jan,

doi = "10.1111/j.1460-9568.2008.06543.x",

language = "English",

volume = "29",

pages = "97--103",

journal = "European Journal of Neuroscience",

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Lucassen, PJ, Bosch, OJ, Jousma, E, Kroemer, SA, Andrew, R , Seckl, JR & Neumann, ID 2009, 'Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11 beta-hydroxysteroid dehydrogenase type 2', European Journal of Neuroscience, vol. 29, no. 1, pp. 97-103. https://doi.org/10.1111/j.1460-9568.2008.06543.x

Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11 beta-hydroxysteroid dehydrogenase type 2. / Lucassen, P. J.; Bosch, O. J.; Jousma, E. et al.
In: European Journal of Neuroscience, Vol. 29, No. 1, 01.2009, p. 97-103.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11 beta-hydroxysteroid dehydrogenase type 2

AU - Lucassen, P. J.

AU - Bosch, O. J.

AU - Jousma, E.

AU - Kroemer, S. A.

AU - Andrew, R.

AU - Seckl, J. R.

AU - Neumann, I. D.

PY - 2009/1

Y1 - 2009/1

N2 - 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 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-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 11 beta-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 11 beta-HSD2 activity after stress rather than by different maternal corticosterone responses. Hence, stress-induced placental 11 beta-HSD2 expression may be critical in protecting the fetal brain from maternal stress-induced effects on adult neurogenesis.

AB - 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 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-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 11 beta-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 11 beta-HSD2 activity after stress rather than by different maternal corticosterone responses. Hence, stress-induced placental 11 beta-HSD2 expression may be critical in protecting the fetal brain from maternal stress-induced effects on adult neurogenesis.

KW - depression

KW - doublecortin

KW - early life

KW - hippocampus

KW - HPA axis

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U2 - 10.1111/j.1460-9568.2008.06543.x

DO - 10.1111/j.1460-9568.2008.06543.x

M3 - Article

SN - 0953-816X

VL - 29

SP - 97

EP - 103

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

IS - 1

ER -

Prenatal stress reduces postnatal neurogenesis in rats selectively bred for high, but not low, anxiety: possible key role of placental 11 beta-hydroxysteroid dehydrogenase type 2

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