title: Regulatory functions of limbic Y1 receptors in body weight and anxiety uncovered by conditional knockout and maternal care.
abstract: 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.
authors.affiliation: Neuroscience Institute of the Cavalieri-Ottolenghi Foundation, Regione Gonzole 10, University of Turin, 10043 Orbassano, Turin, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bertocchi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Oberto
authors.forename: Angela
authors.initials: A
authors.lastname: Longo
authors.forename: Paolo
authors.initials: P
authors.lastname: Mele
authors.forename: Marianna
authors.initials: M
authors.lastname: Sabetta
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bartolomucci
authors.forename: Paola
authors.initials: P
authors.lastname: Palanza
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.forename: Carola
authors.initials: C
authors.lastname: Eva
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000235:genetics*; D001835:Body Weight / Q000235:genetics*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D055786:Gene Knockout Techniques; D017403:In Situ Hybridization; D020738:Leptin / Q000097:blood; D008032:Limbic System / Q000378:metabolism*; D008124:Locomotion / Q000502:physiology; D008425:Maternal Behavior / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016548:Prosencephalon / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000235:genetics*
chemical_list: D020738:Leptin; C507698:Npy1r protein, mouse; D017476:Receptors, Neuropeptide Y; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
references.citation: Ann N Y Acad Sci. 2004 Jun;1018:35-45
references.pmid: 15240350
references.citation: Neuropsychopharmacology. 2005 Dec;30(12):2192-204
references.pmid: 15920504
references.citation: Ann Neurol. 2008 Sep;64(3):284-93
references.pmid: 18825662
references.citation: Physiol Behav. 2006 Oct 30;89(3):320-8
references.pmid: 16842828
references.citation: Science. 1996 Dec 6;274(5293):1678-83
references.pmid: 8939850
references.citation: Endocrinology. 2003 Jan;144(1):281-91
references.pmid: 12488356
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18632-7
references.pmid: 16339312
references.citation: Epigenetics. 2007 Jan-Mar;2(1):22-8
references.pmid: 17965624
references.citation: Physiol Behav. 2001 Jun;73(3):255-60
references.pmid: 11438350
references.citation: Biol Psychiatry. 2006 Apr 1;59(7):660-3
references.pmid: 16325152
references.citation: Neuropharmacology. 2002 May;42(6):798-806
references.pmid: 12015206
references.citation: Neurosci Biobehav Rev. 2007;31(1):3-17
references.pmid: 16950513
references.citation: Endocrinology. 2007 Aug;148(8):3666-73
references.pmid: 17463058
references.citation: Nat Neurosci. 2000 Aug;3(8):799-806
references.pmid: 10903573
references.citation: Behav Brain Res. 2006 Feb 15;167(1):87-93
references.pmid: 16203045
references.citation: Trends Mol Med. 2007 Jul;13(7):269-77
references.pmid: 17544850
references.citation: Eur J Neurosci. 2000 Apr;12(4):1319-30
references.pmid: 10762361
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15659-64
references.pmid: 9861026
references.citation: J Neurosci. 2008 Jan 23;28(4):893-903
references.pmid: 18216197
references.citation: Front Neuroendocrinol. 2006 Sep;27(3):308-39
references.pmid: 16989896
references.citation: Nature. 2008 Apr 24;452(7190):997-1001
references.pmid: 18385673
references.citation: Crit Rev Neurobiol. 1993;7(2):89-162
references.pmid: 8102325
references.citation: J Neurosci. 2004 Nov 17;24(46):10568-78
references.pmid: 15548671
references.citation: Eur Neuropsychopharmacol. 2010 Mar;20(3):164-75
references.pmid: 19781916
references.citation: Neuropsychopharmacology. 1993 Jun;8(4):357-63
references.pmid: 8099792
references.citation: PLoS One. 2007 Jun 20;2(6):e533
references.pmid: 17579707
references.citation: Pharmacol Biochem Behav. 2002 Aug;73(1):147-58
references.pmid: 12076734
references.citation: J Comp Neurol. 2003 Sep 22;464(3):285-311
references.pmid: 12900925
references.citation: Neurosci Biobehav Rev. 2001 May;25(3):235-60
references.pmid: 11378179
references.citation: Endocrinology. 2000 Mar;141(3):1011-6
references.pmid: 10698177
references.citation: J Comp Neurol. 2011 May 1;519(7):1219-57
references.pmid: 21452195
references.citation: Brain Res Brain Res Rev. 1998 May;26(2-3):154-66
references.pmid: 9651513
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8938-43
references.pmid: 12072562
references.citation: Stress. 2006 Mar;9(1):21-8
references.pmid: 16753930
references.citation: Reprod Toxicol. 2007 Jul;24(1):9-19
references.pmid: 17561370
references.citation: Neuropeptides. 2004 Aug;38(4):267-75
references.pmid: 15337379
references.citation: Endocrinology. 2004 Jun;145(6):2702-6
references.pmid: 15044366
references.citation: Behav Pharmacol. 1995 Apr;6(3):215-222
references.pmid: 11224329