title: Reduced NPY Y1 receptor hippocampal expression and signs of decreased vagal modulation of heart rate in mice.
abstract: Central neuropeptide Y (NPY) signaling participates in the regulation of cardiac autonomic outflow, particularly via activation of NPY-Y1 receptors (Y1Rs). However, the specific brain areas and neural pathways involved have not been completely identified yet. Here, we evaluate the role of hippocampal Y1Rs in the modulation of the autonomic control of cardiac function using a conditional knockout mouse model. Radiotelemetric transmitters were implanted in 4-month-old male mice exhibiting reduced forebrain expression (rfb) of the Y1R (Npy1rrfb, n=10) and their corresponding controls (Npy1r2lox, n=8). ECG signals were recorded (i) during resting conditions, (ii) under selective pharmacological manipulation of cardiac vagal activity, and (iii) during acute and chronic psychosocial stress challenges, and analyzed via time- and frequency-domain analysis of heart rate variability. Npy1rrfbmice showed a lower Npy1r mRNA density in the dentate gyrus and in the CA1 region of the hippocampus. Under resting undisturbed conditions, Npy1rrfbmice exhibited (i) a higher heart rate, (ii) a reduced overall heart rate variability, and (iii) lower values of the indices of vagal modulation compared to Npy1r2loxcounterparts. Following pharmacological vagal inhibition, heart rate was higher in control but not in Npy1rrfbmice compared to their respective baseline values, suggesting that tonic vagal influences on heart rate were reduced in Npy1rrfbmice. The magnitude of the heart rate response to acute stressors was smaller in Npy1rrfbmice compared to Npy1r2loxcounterparts, likely due to a concurrent lower vagal withdrawal. These findings suggest that reduced Y1R expression leads to a decrease in resting vagal modulation and heart rate variability, which, in turn, may determine a reduced cardiac autonomic responsiveness to acute stress challenges.
authors.affiliation: Department of Neuroscience, University of Parma, Italy.
authors.forename: Rosario
authors.initials: R
authors.lastname: Statello
authors.affiliation: Department of Neuroscience, University of Parma, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Carnevali
authors.affiliation: Department of Neuroscience, University of Parma, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Paterlini
authors.affiliation: Department of Neuroscience, University of Parma, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Gioiosa
authors.affiliation: Neuroscience Institute Cavalieri-Ottolenghi Foundation, University of Turin, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bertocchi
authors.affiliation: Neuroscience Institute Cavalieri-Ottolenghi Foundation, University of Turin, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Oberto
authors.affiliation: Neuroscience Institute Cavalieri-Ottolenghi Foundation, University of Turin, Italy.
authors.forename: Carola
authors.initials: C
authors.lastname: Eva
authors.affiliation: Department of Neuroscience, University of Parma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Palanza
authors.affiliation: Department of Neuroscience, University of Parma, Italy. Electronic address: andrea.sgoifo@unipr.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sgoifo
mesh_terms: D000818:Animals; D006339:Heart Rate / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019832:N-Methylscopolamine / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000096:biosynthesis* / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology; D013686:Telemetry; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
chemical_list: D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D019832:N-Methylscopolamine
keywords: Autonomic; Heart; Knockout; NPY; Parasympathetic; Stress