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Publication : Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care.

First Author  Bertocchi I Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  48 Pages  19395-400
PubMed ID  22084082 Mgi Jnum  J:180396
Mgi Id  MGI:5306199 Doi  10.1073/pnas.1109468108
Citation  Bertocchi I, et al. (2011) Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care. Proc Natl Acad Sci U S A 108(48):19395-400
abstractText  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 (Npy1r(rfb)). Npy1r(rfb) mice exhibited increased anxiety and reduced body weight, less adipose tissue, and lower serum leptin levels. Npy1r(rfb) 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 Npy1r(rfb) and Npy1r(2lox) 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.
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