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Deep breath and relax: a study of NPS/NPSR1

Zhu, Hongyan
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1298324376

Abstract Details

2011, PhD, University of Cincinnati, Medicine: Developmental Biology.
Asthma is a complex disorder involving the interaction between host genetic susceptibility and environmental factors. Psychological stress contributes to the exacerbation of asthma. NPSR1 has been linked with asthma, including airway hyperresponsiveness (AHR) and panic disorders, by a genomic association study. In this thesis, we aimed to characterize the role of NPSR1 in pulmonary and stress responses. We examined the Npsr1-deficient mice in two models of asthma and found that Npsr1 deletion had no impact on airway inflammation or airway hyperresponsiveness (AHR) in ovalbumin- or Aspergillus fumigatus-induced experimental asthma. Further, Npsr1 had a very low level of expression, based on RT-PCR analysis, in the basal or allergen-challenged lung, supporting that NPSR1’s direct role in the lung may be limited. Behavioral studies revealed that Npsr1-deficient mice had an impaired stress response and failed to show increases in locomotion, anxiolysis, or corticosterone release induced by intracerebroventricular (ICV) administration of neuropeptide S (NPS), the putative endogenous ligand of NPSR1, suggesting that NPS/NPSR1 signaling is involved in stress response and has anxiolytic effect. Nps and Npsr1 are expressed in brain regions that regulate respiratory rhythm, and clinical evidence show association of respiration changes with psychological stress and emotional diseases. Thus, we investigated whether NPS/NPSR1 regulated respiratory function through a central-mediated pathway. Analysis of breathing patterns by whole-body plethysmography revealed that ICV NPS, as compared with the artificial cerebrospinal fluid control, increased respiratory frequency and decreased tidal volume in an NPSR1-dependent manner but did not affect enhanced pause (Penh), a parameter that correlates with lung obstruction. Following serial methacholine inhalation, ICV NPS increased respiratory frequency in WT mice, but not Npsr1-deficient mice, and had no effect on tidal volume. ICV NPS significantly reduced AHR to methacholine as measured by whole-body plethysmography, whereas ICV NPS did not alter airway mechanics in response to methacholine as measured by invasive plethysmography. Collectively, these data support the hypothesis that NPS and NPSR1 regulate respiratory functions likely via a central-mediated pathway suggesting that a central nervous system pathway may potentially mediate the underlying association of NPSR1 with asthma and AHR.
Marc Rothenberg, MDPhD (Committee Chair)
Michael Williams, PhD (Committee Member)
Charles Vorhees, PhD (Committee Member)
David Hildeman, PhD (Committee Member)
Simon Hogan, PhD (Committee Member)
Timothy Lecras, PhD (Committee Member)
160 p.
Biology
neuropeptide S; neuropeptide S receptor 1; stress; respiration; asthma; anxiety

Recommended Citations

Citations

  • Zhu, H. (2011). Deep breath and relax: a study of NPS/NPSR1 [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1298324376

    APA Style (7th edition)

  • Zhu, Hongyan. Deep breath and relax: a study of NPS/NPSR1. 2011. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1298324376.

    MLA Style (8th edition)

  • Zhu, Hongyan. "Deep breath and relax: a study of NPS/NPSR1." Doctoral dissertation, University of Cincinnati, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1298324376

    Chicago Manual of Style (17th edition)

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This open access ETD is published by University of Cincinnati and OhioLINK.