Ontogeny of the HPA axis of the CD1 mouse following 24 h maternal deprivation at pnd 3.
One of the striking characteristics of the developing neuroendocrine system of rats and mice is the stress hypo-responsive period (SHRP), i.e. low basal corticosterone secretion and the inability to increase corticosterone in response to mild stressors during the first 2 weeks of life. However, immediately after 24 h of deprivation from maternal care the response of the hypothalamic-pituitary-adrenal (HPA) axis to mild stressors is enhanced. This study examines in CD1 mouse pups the recovery pattern of markers of HPA axis (re)activity from maternal deprivation (once for 24 h from postnatal days (pnds) 3 to 4). As expected, deprivation induced a profound corticosterone response to novelty immediately after deprivation. In contrast, 1 day after reunion with the mother (pnd 5), this effect was abolished, lasting for at least 3 days. Basal corticosterone remained even below control levels. Corticotropin-releasing hormone (CRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) was suppressed for 2 days, exceeded control levels at pnds 7 and 8, and subsequently followed the gradual decline observed in controls until pnd 12. Delayed and rather short-lasting changes were found for adrenocorticotropic hormone (low at pnd 5), and glucocorticoid receptor mRNA expression (decreased in the PVN at pnd 4, and in the hippocampal CA1 area at pnd 5). Hippocampal mineralocorticoid receptor mRNA expression was unaffected. From pnds 9 to 13, both deprived and control pups gradually emerged from the SHRP in a similar temporal pattern. In conclusion, maternal deprivation at pnd 3 augments hypo-responsiveness of corticosterone secretion to mild stress for several days, but does not affect the duration of the SHRP. Whether CRH and glucocorticoid receptor changes are cause or consequence remains to be established.
Enthoven
L
L
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Leiden University Medical Center, Leiden University, The Netherlands.
Schmidt
M V
MV
Cheung
Y H
YH
van der Mark
M H
MH
de Kloet
E R
ER
Oitzl
M S
MS
D000818:Animals; D000831:Animals, Newborn; D001010:Anxiety, Separation / Q000503:physiopathology*; D003345:Corticosterone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D051379:Mice; D009035:Mothers; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*
D003345:Corticosterone