title: Immediate Effects of Maternal Deprivation on the (Re)Activity of the HPA-Axis Differ in CD1 and C57Bl/6J Mouse Pups.
abstract: The postnatal development of the mouse is characterized by a period of hypo-responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis to mild stressors. Maternal deprivation (MD) during this period can disrupt the quiescence of the HPA-axis. The present study examined the influence of strain (outbred CD1 vs. inbred C57BL/6J mice) on some central and peripheral components of the HPA-axis in neonatal mice (5-day-old) in the presence of their mother or after 24 h MD (on postnatal day 4) under basal or mild stressful conditions. In the presence of the dam, adrenal corticosterone (CORT) secretion was low in both mouse strains. Compared to CD1 mice, C57BL/6J had lower CORT levels associated with higher ACTH levels and ACTH/CORT ratio (i.e., lower adrenal sensitivity to ACTH), and higher glucocorticoid receptor (GR) mRNA expression in the paraventricular nucleus. Although MD disinhibited the HPA-axis in both strains as reflected by increased basal CORT and ACTH, we found a strain-dependent pattern. MD increased CORT more in C57BL/6J compared to CD1 mice together with a lower ACTH/CORT ratio (i.e., higher adrenal sensitivity to ACTH), while GR mRNA was no longer different in the two strains. However, this increased adrenal sensitivity in maternally deprived C57BL/6J mice was not reflected in their CORT response to a subsequent novelty stressor, possibly due to an MD-induced ceiling effect in their steroidogenic capacity. In conclusion, the immediate outcome of MD depends on the genetic background of the mother-infant dyad, suggesting that maybe also the outcome in later-life cannot be generalized.
authors.affiliation: Division of Medical Pharmacology, Leiden Academic Center for Drug Research, Leiden University , Leiden , Netherlands ; Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden University , Leiden , Netherlands ; Traumatic Stress Studies Division, Department of Psychiatry, Icahn School of Medicine at Mount Sinai , New York, NY , USA ; Laboratory of Molecular Neuropsychiatry, Department of Psychiatry, Icahn School of Medicine at Mount Sinai , New York, NY , USA ; PTSD Research Program, Mental Health Patient Care Center, James J. Peters Veterans Affairs Medical Center , Bronx, NY , USA.
authors.forename: Nikolaos P
authors.initials: NP
authors.lastname: Daskalakis
authors.affiliation: Division of Medical Pharmacology, Leiden Academic Center for Drug Research, Leiden University , Leiden , Netherlands.
authors.forename: Leo
authors.initials: L
authors.lastname: Enthoven
authors.affiliation: Division of Medical Pharmacology, Leiden Academic Center for Drug Research, Leiden University , Leiden , Netherlands.
authors.forename: Edwige
authors.initials: E
authors.lastname: Schoonheere
authors.affiliation: Division of Medical Pharmacology, Leiden Academic Center for Drug Research, Leiden University , Leiden , Netherlands ; Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden University , Leiden , Netherlands.
authors.forename: Edo Ronald
authors.initials: ER
authors.lastname: de Kloet
authors.affiliation: Division of Medical Pharmacology, Leiden Academic Center for Drug Research, Leiden University , Leiden , Netherlands ; Center for Neuroscience, Swammerdam Institute for Life Sciences, University of Amsterdam , Amsterdam , Netherlands.
authors.forename: Melly S
authors.initials: MS
authors.lastname: Oitzl
keywords: ACTH; CRH; GR; corticosterone; genetic; hypothalamic–pituitary–adrenal axis; maternal deprivation; neonate