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A singleday treatment with mifepristone is sufficient to normalize chronic glucocorticoid induced suppression of hippocampal cell proliferation. PLoS One (2012)

by P Hu, C Oomen, van Dam AM, J Wester, Zhou JN, M Joels
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Age- and sex-dependent effects of early life stress on hippocampal neurogenesis

by Manila Loi , Sylwia Koricka , Paul J Lucassen , Marian Joëls , Manila Loi
"... Age-and sex-dependent effects of early life stress on hippocampal neurogenesis Loi, M.; Koricka, S.; Lucassen, P.J.; Joëls, M. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than ..."
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Age-and sex-dependent effects of early life stress on hippocampal neurogenesis Loi, M.; Koricka, S.; Lucassen, P.J.; Joëls, M. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Early life stress is a well-documented risk factor for the development of psychopathology in genetically predisposed individuals. As it is hard to study how early life stress impacts human brain structure and function, various animal models have been developed to address this issue. The models discussed here reveal that perinatal stress in rodents exerts lasting effects on the stress system as well as on the structure and function of the brain. One of the structural parameters strongly affected by perinatal stress is adult hippocampal neurogenesis. Based on compiled literature data, we report that postnatal stress slightly enhances neurogenesis until the onset of puberty in male rats; when animals reach adulthood, neurogenesis is reduced as a consequence of perinatal stress. By contrast, female rats show a prominent reduction in neurogenesis prior to the onset of puberty, but this effect subsides when animals reach young adulthood. We further present preliminary data that transient treatment with a glucocorticoid receptor antagonist can normalize cell proliferation in maternally deprived female rats, while the compound had no effect in non-deprived rats. Taken together, the data show that neurogenesis is affected by early life stress in an age-and sex-dependent manner and that normalization may be possible during critical stages of brain development.
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...is, we performed a pilot study in which female rats, exposed to maternal deprivation at PND 3, were treated during a critical developmental window with the GR antagonist mifepristone. We selected the period of PND 26–28 for treatment with mifepristone, as earlier studies have shown that interventions at this stage of development have significant consequences for the development of the brain and the response to stress later in life (84). Moreover, we had demonstrated before that even a brief treatment with mifepristone is very powerful in normalizing the effects of chronic stress in adult rats (77). As shown in Figure 4, the number of Ki67-positive cells was significantly higher in the hilus (but not in the DG as a whole, data not shown) in MD rats treated with mifepristone compared to those treated with vehicle, whereas the drug did not affect the number of Ki67-positive cells in non-deprived rats. Similarly, mifepristone treatment tended to cause higher levels of DCX-positive cells in the dentate supra-pyramidal blade of MD rats compared to vehicle treated MD controls, although this did not reach significance (p= 0.08); mifepristone did not affect the number of DCX-positive cells in n...

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