title: Neuropeptide Y mediates the initial hypothalamic-pituitary-adrenal response to maternal separation in the neonatal mouse.
abstract: The function of the hypothalamic-pituitary-adrenal (HPA) axis of the neonatal mouse or rat is characterized by a period of quiescence, where mild stimuli are unable to elicit a pronounced increase in circulating corticosterone. A disruption of this period by maternal separation has been shown to result in a variety of long-term consequences, including neuroendocrine and behavioral disturbances. We have recently shown that peripheral metabolic markers like glucose or ghrelin are altered by maternal separation and that these changes precede the effects on corticosterone secretion. In the current study, we investigated whether the initial activation of the HPA axis is mediated via neuropeptide Y (NPY). To test this hypothesis, we studied the effects of an 8 h maternal separation in NPY-deficient mice. In addition, we compared the effect of the genotype with the previously described pharmacological effect of a ghrelin receptor antagonist. We could show that the peripheral response to maternal separation is decreased in NPY heterozygous and homozygous animals. In addition, maternal separation effects on corticotropin releasing hormone and glucocorticoid receptor expression in the brain were prevented in NPY-deficient pups. These effects were similar to a pharmacological ghrelin receptor blockade. We conclude that metabolic signals via an NPY-mediated pathway play a crucial role in activating the stress system of the neonatal mouse.
authors.affiliation: Max Planck Institute of Psychiatry, RG Molecular Stress Physiology, Kraepelinstr. 2-10, 80804 Munich, Germany. mschmidt@mpipsykl.mpg.de
authors.forename: Mathias V
authors.initials: MV
authors.lastname: Schmidt
authors.forename: Claudia
authors.initials: C
authors.lastname: Liebl
authors.forename: Vera
authors.initials: V
authors.lastname: Sterlemann
authors.forename: Karin
authors.initials: K
authors.lastname: Ganea
authors.forename: Jakob
authors.initials: J
authors.lastname: Hartmann
authors.forename: Daniela
authors.initials: D
authors.lastname: Harbich
authors.forename: Stephanie
authors.initials: S
authors.lastname: Alam
authors.forename: Marianne B
authors.initials: MB
authors.lastname: Müller
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001127:Arginine Vasopressin / Q000235:genetics; D001483:Base Sequence; D001786:Blood Glucose / Q000032:analysis; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008426:Maternal Deprivation; D051379:Mice; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics
chemical_list: D001786:Blood Glucose; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone