title: Effects of early-life stress on cognitive function and hippocampal structure in female rodents.
abstract: We tested the effect of early-life stress (ELS) - 24h maternal deprivation (MD) at postnatal day (PND) 3 - on cognitive performance and hippocampal structure in 12-17-week-old female rats. Behavioral performance was examined in: the Elevated Plus Maze, as an index for general anxiety; the rodent Iowa gambling test, probing reward-based decision making; and the object recognition and object-in-location task, to assess non-stressful contextual memory performance. We further determined hippocampal dentate gyrus (DG) volume and cell density as well as adult proliferation and neurogenesis rates. Half of the rats was treated with the glucocorticoid receptor antagonist mifepristone during a critical pre-pubertal developmental window (PNDs 26-28), in an attempt to ameliorate the potentially adverse behavioral consequences of ELS. Neither MD nor treatment with the glucocorticoid antagonist affected behavioral performance of the females in any of the tasks. Also, DG structure, proliferation and neurogenesis were not different between the groups. Lack of structural differences and a behavioral phenotype in non-stressful hippocampus dependent learning tasks fits with the lack of phenotype generally reported after ELS in female but less so in male rodents. As evident from an extensive literature review, female and male animals appear to respond more similarly to early-life adversity when tested in anxiety-related tasks. This agrees with recent findings in humans suggesting that females may be relatively resilient to the structural/hippocampal effects of childhood maltreatment, but not to the anxiety and mood-related psychopathology for which childhood maltreatment is considered a risk factor.
authors: Department of Translational Neuroscience, Brain Center Rudolf Magnus, UMC Utrecht, The Netherlands.
authors: M
authors: M
authors: Loi
authors: Department of Translational Neuroscience, Brain Center Rudolf Magnus, UMC Utrecht, The Netherlands.
authors: J C L
authors: JC
authors: Mossink
authors: SILS-Center for Neuroscience, University of Amsterdam, The Netherlands.
authors: G F
authors: GF
authors: Meerhoff
authors: SILS-Center for Neuroscience, University of Amsterdam, The Netherlands.
authors: J L
authors: JL
authors: Den Blaauwen
authors: SILS-Center for Neuroscience, University of Amsterdam, The Netherlands. Electronic address: p.j.lucassen@uva.nl.
authors: P J
authors: PJ
authors: Lucassen
authors: Department of Translational Neuroscience, Brain Center Rudolf Magnus, UMC Utrecht, The Netherlands. Electronic address: m.joels@umcutrecht.nl.
authors: M
authors: M
authors: Joëls
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005715:Gambling / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology*; D006727:Hormone Antagonists / Q000494:pharmacology; D008426:Maternal Deprivation; D008568:Memory / Q000187:drug effects / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D011897:Random Allocation; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D012741:Sexual Maturation; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D017211:Treatment Failure
chemical_list: D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone
keywords: contextual memory; depression; hippocampus; neurogenesis; prefrontal cortex; sex difference