Conditional Inactivation of Neuropeptide Y Y1 Receptors Unravels the Role of Y1 and Y5 Receptors Coexpressing Neurons in Anxiety

Longo, Angela; Marrama, P; Bertocchi, Ilaria; Oberto, Alessandra; Bachmann, Annette; Bartolomucci, Alessandro; Palanza, Paola; Sprengel, Rolf; Eva, Carola

doi:10.1016/j.biopsych.2014.01.009

Cited by 29 publications

(32 citation statements)

References 33 publications

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“…We have previously shown that the conditional inactivation of Npy1r selectively in neurons coexpressing Y5R increases anxiety but is not associated with the activation of HPA-axis activity (Longo et al 2014). In the present study, we further demonstrated that Npy1r Y5R−/− conditional mutants display a strong anxious phenotype in the EPM and OF, independently of housing conditions, but show identical levels of CRH in the CeA and PVNmp, of GR in the CA1 and of corticosterone serum levels, compared to their control littermates.…”

Section: Discussionmentioning

confidence: 99%

“…B6129S (129/SvJ, C57BL/6N derived strain) mice was achieved as previously described (Longo et al 2014). Briefly, a targeting vector for homologous recombination in embryonic stem (ES) cells was designed to introduce loxP sites around exons 2-3, which code for the entire region of Npy1r, and a frt-neo-frt cassette ≈ 450 bp excised from p146 (kind gift of William Wisden) upstream the ATG of Npy1r exon 2.…”

Section: Y5r−/−mentioning

confidence: 99%

“…Four different 40-/45-mer oligonucleotide S35-labeled probes were simultaneously used to increase the signal and the reaction was carried out as previously described (Longo et al 2014), according to the protocol reported by Wisden and Morris (2002). The area of interest of clearly distinguishable nuclei was defined following the boundaries of the labeled regions [CA1 pyramidal cell layer (CA1), dentate gyrus granule cell layer (DG)], while three to four spots were used for each slice in poorly contrasted regions [BLA and CA3 pyramidal cell layer (CA3)].…”

Section: In Situ Hybridization For Npy1r Mrnamentioning

confidence: 99%

“…Immunostaining of Y1R was carried on free-floating vibratome-cut brain coronal sections (50 μm) as previously described (Longo et al 2014). Primary Y1R antibody was kindly provided by Janice Urban and was used at 1:2000 dilution.…”

Section: Immunofluorescencementioning

confidence: 99%

“…In the rodent brain, the Y1R colocalizes with Y5 receptor (Y5R) in the hippocampus and basolateral amygdala (BLA; Oberto et al 2007;Wolak et al 2003) where they have overlapping functions in regulating anxiety (Sorensen et al 2004). We previously showed that conditional inactivation of Npy1r restricted to Y5R-containing neurons in adult Npy1r Y5R−/− mice increased anxiety without affecting basal or acute stress-activated hypothalamus-pituitary-adrenocortical (HPA) axis activity (Longo et al 2014). These data suggest that NPY, acting on Y1R, might activate distinct neuronal circuits to regulate anxiety-related behaviors and stress responses.…”

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confidence: 99%

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NPY‐Y1 coexpressed with NPY‐Y5 receptors modulate anxiety but not mild social stress response in mice

Longo

Oberto

Marrama

et al. 2015

Genes Brain and Behavior

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The Y1 and Y5 receptors for neuropeptide Y have overlapping functions in regulating anxiety. We previously demonstrated that conditional removal of the Y1 receptor in the Y5 receptor expressing neurons in juvenile Npy1r Y5R−/− mice leads to higher anxiety but no changes in hypothalamus-pituitary-adrenocortical axis activity, under basal conditions or after acute restraint stress. In the present study, we used the same conditional system to analyze the specific contribution of limbic neurons coexpressing Y1 and Y5 receptors on the emotional and neuroendocrine responses to social chronic stress, using different housing conditions (isolation vs. group-housing) as a model. We demonstrated that control Npy1r 2lox male mice housed in groups show increased anxiety and hypothalamus-pituitary-adrenocortical axis activity compared with Npy1r 2lox mice isolated for six weeks immediately after weaning. Conversely, Npy1r Y5R−/− conditional mutants display an anxious-like behavior but no changes in hypothalamus-pituitary-adrenocortical axis activity as compared with their control littermates, independently of housing conditions. These results suggest that group housing constitutes a mild social stress for our B6129S mouse strain and they confirm that the conditional inactivation of Y1 receptors specifically in Y5 receptor containing neurons increases stress-related anxiety without affecting endocrine stress responses.

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Section: Discussionmentioning

confidence: 99%

Section: Y5r−/−mentioning

confidence: 99%