Proceedings of the National Academy of Sciences - PNAS, 2011-11, Vol.108 (48), p.19395-19400
2011
Details
- Autor(en) / Beteiligte
- Titel
- Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2011-11, Vol.108 (48), p.19395-19400
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- Elektronische Zeitschriftenbibliothek (Open access)
- Beschreibungen/Notizen
- Neuropeptide Y (NPY) plays an important role in stress, anxiety, obesity, and energy homeostasis via activation of NPY-Y1 receptors (Y1Rs) in the brain. However, global knockout of the Npy1r gene has low or no impact on anxiety and body weight. To uncover the role of limbic Y1Rs, we generated conditional knockout mice in which the inactivation of the Npy1r gene was restricted to excitatory neurons of the forebrain, starting from juvenile stages (Npy1rrfb). Npy1rrfb mice exhibited increased anxiety and reduced body weight, less adipose tissue, and lower serum leptin levels. Npy1rrfb mutants also had a hyperactive hypothalamic–pituitary–adrenocortical axis, as indicated by higher peripheral corticosterone and higher density of NPY immunoreactive fibers and corticotropin releasing hormone immunoreactive cell bodies in the paraventricular hypothalamic nucleus. Importantly, through fostering experiments, we determined that differences in phenotype between Npy1rrfb and Npy1r2lox mice became apparent when both genotypes were raised by FVB/J but not by C57BL/6J dams, suggesting that limbic Y1Rs are key targets of maternal care-induced programming of anxiety and energy homeostasis.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.1109468108Titel-ID: cdi_pnas_primary_108_48_19395
- Format
- –
- Schlagworte
- adipose tissue, Age Factors, Analysis of Variance, Animals, Anxiety, Anxiety - genetics, Biological Sciences, Body weight, Body Weight - genetics, corticosterone, Corticosterone - blood, corticotropin, Corticotropin-Releasing Hormone - metabolism, Dams, energy, Forebrain, Gene Knockout Techniques, genes, genotype, Genotypes, homeostasis, In Situ Hybridization, leptin, Leptin - blood, Limbic System - metabolism, Locomotion - physiology, Maternal Behavior - physiology, Mice, Mice, Inbred Strains, Mice, Transgenic, Mothers, mutants, Neurochemistry, Neurons, neuropeptide Y, Neuropeptides, Neuropsychology, obesity, paraventricular hypothalamic nucleus, Peptides, phenotype, Prosencephalon - metabolism, Receptors, Receptors, Neuropeptide Y - genetics, Rodents, Weight