Fetal brain 11β-hydroxysteroid dehydrogenase type 2 selectively determines programming of adult depressive-like behaviors and cognitive function, but not anxiety behaviors in male mice.

Autor: Wyrwoll C; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom; School of Anatomy, Physiology & Human Biology, The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia., Keith M; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom., Noble J; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom., Stevenson PL; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom., Bombail V; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom., Crombie S; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom., Evans LC; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom., Bailey MA; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom., Wood E; Centre for Cognitive and Neural Systems, University of Edinburgh, EH8 9JZ, United Kingdom., Seckl JR; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom., Holmes MC; UoE/BHF Centre for Cardiovascular Science, University of Edinburgh, EH16 4TJ, United Kingdom. Electronic address: megan.holmes@ed.ac.uk.
Jazyk: angličtina
Zdroj: Psychoneuroendocrinology [Psychoneuroendocrinology] 2015 Sep; Vol. 59, pp. 59-70. Date of Electronic Publication: 2015 May 18.
DOI: 10.1016/j.psyneuen.2015.05.003
Abstrakt: Stress or elevated glucocorticoids during sensitive windows of fetal development increase the risk of neuropsychiatric disorders in adult rodents and humans, a phenomenon known as glucocorticoid programming. 11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2), which catalyses rapid inactivation of glucocorticoids in the placenta, controls access of maternal glucocorticoids to the fetal compartment, placing it in a key position to modulate glucocorticoid programming of behavior. However, the importance of the high expression of 11β-HSD2 within the midgestational fetal brain is unknown. To examine this, a brain-specific knockout of 11β-HSD2 (HSD2BKO) was generated and compared to wild-type littermates. HSD2BKO have markedly diminished fetal brain 11β-HSD2, but intact fetal body and placental 11β-HSD2 and normal fetal and placental growth. Despite normal fetal plasma corticosterone, HSD2BKO exhibit elevated fetal brain corticosterone levels at midgestation. As adults, HSD2BKO show depressive-like behavior and have cognitive impairments. However, unlike complete feto-placental deficiency, HSD2BKO show no anxiety-like behavioral deficits. The clear mechanistic separation of the programmed components of depression and cognition from anxiety implies distinct mechanisms of pathogenesis, affording potential opportunities for stratified interventions.
(Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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