Differential neurodegenerative phenotypes are associated with heterogeneous voiding dysfunction in a coronavirus-induced model of multiple sclerosis
Identifieur interne : 000158 ( Pmc/Curation ); précédent : 000157; suivant : 000159Differential neurodegenerative phenotypes are associated with heterogeneous voiding dysfunction in a coronavirus-induced model of multiple sclerosis
Auteurs : Sanghee Lee [États-Unis] ; Balachandar Nedumaran ; Joseph Hypolite ; Brian Caldwell ; Michael C. Rudolph ; Anna P. MalykhinaSource :
- Scientific Reports [ 2045-2322 ] ; 2019.
Abstract
Patients with multiple sclerosis (MS) develop a variety of lower urinary tract symptoms (LUTS). We previously characterized a murine model of neurogenic bladder dysfunction induced by a neurotropic strain of a coronavirus. In the present study, we further study the role of long-lasting neurodegeneration on the development of neurogenic bladder dysfunction in mice with corona-virus induced encephalitis (CIE). Long-term follow up study revealed three phenotypes of neurodegenerative symptom development: recovery (REC group), chronic progression (C-PRO group) and chronic disease with relapsing-remitting episodes (C-RELAP group). The levels of IL-1β in REC group, IL-10 in C-RELAP group, and IL-1β, IL-6, IL-10 and TNF-α in C-PRO group were diminished in the brain. The levels of TNF-α in REC group and INF-γ, IL-2, TGF-β and TNF-α in the C-PRO group were also diminished in the urinary bladder. Mice in C-RELAP group showed a delayed recovery of voiding function.
Url:
DOI: 10.1038/s41598-019-47407-x
PubMed: 31350464
PubMed Central: 6659655
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Balachandar Nedumaran<affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Urology, Department of Surgery,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Urology, Department of Surgery,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Urology, Department of Surgery,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Endocrinology, Metabolism & Diabetes,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>NORC Metabolic and Cellular Analysis Core Center for Women’s Health Research,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>NORC Metabolic and Cellular Analysis Core Center for Women’s Health Research,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Urology, Department of Surgery,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation>Le document en format XML
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Rudolph</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Endocrinology, Metabolism & Diabetes,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation><affiliation><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>NORC Metabolic and Cellular Analysis Core Center for Women’s Health Research,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation></author><author><name sortKey="Malykhina, Anna P" sort="Malykhina, Anna P" uniqKey="Malykhina A" first="Anna P." last="Malykhina">Anna P. Malykhina</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Urology, Department of Surgery,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</nlm:aff><wicri:noCountry code="subfield">Co USA</wicri:noCountry></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2019">2019</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Patients with multiple sclerosis (MS) develop a variety of lower urinary tract symptoms (LUTS). We previously characterized a murine model of neurogenic bladder dysfunction induced by a neurotropic strain of a coronavirus. In the present study, we further study the role of long-lasting neurodegeneration on the development of neurogenic bladder dysfunction in mice with corona-virus induced encephalitis (CIE). Long-term follow up study revealed three phenotypes of neurodegenerative symptom development: recovery (REC group), chronic progression (C-PRO group) and chronic disease with relapsing-remitting episodes (C-RELAP group). The levels of IL-1β in REC group, IL-10 in C-RELAP group, and IL-1β, IL-6, IL-10 and TNF-α in C-PRO group were diminished in the brain. The levels of TNF-α in REC group and INF-γ, IL-2, TGF-β and TNF-α in the C-PRO group were also diminished in the urinary bladder. Mice in C-RELAP group showed a delayed recovery of voiding function. <italic>In vitro</italic> contractility studies determined a decreased basal detrusor tone and reduced amplitude of nerve-mediated contractions in C-RELAP group, whereas C-PRO group had elevated muscle-mediated contractions. In conclusion, mice with CIE developed three phenotypes of neurologic impairment mimicking different types of MS progression in humans and showed differential mechanisms driving neurogenic bladder dysfunction.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Campbell, Jd" uniqKey="Campbell J">JD Campbell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fowler, Cj" uniqKey="Fowler C">CJ Fowler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Miller, H" uniqKey="Miller H">H Miller</name></author><author><name sortKey="Simpson, Ca" uniqKey="Simpson C">CA Simpson</name></author><author><name sortKey="Yeates, Wk" uniqKey="Yeates W">WK Yeates</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Betts, Cd" uniqKey="Betts C">CD Betts</name></author><author><name sortKey="D Ellow, Mt" uniqKey="D Ellow M">MT 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Sci Rep</journal-id><journal-id journal-id-type="iso-abbrev">Sci Rep</journal-id><journal-title-group><journal-title>Scientific Reports</journal-title></journal-title-group><issn pub-type="epub">2045-2322</issn><publisher><publisher-name>Nature Publishing Group UK</publisher-name><publisher-loc>London</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">31350464</article-id><article-id pub-id-type="pmc">6659655</article-id><article-id pub-id-type="publisher-id">47407</article-id><article-id pub-id-type="doi">10.1038/s41598-019-47407-x</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Differential neurodegenerative phenotypes are associated with heterogeneous voiding dysfunction in a coronavirus-induced model of multiple sclerosis</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Sanghee</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Nedumaran</surname><given-names>Balachandar</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Hypolite</surname><given-names>Joseph</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Caldwell</surname><given-names>Brian</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-6147-212X</contrib-id><name><surname>Rudolph</surname><given-names>Michael C.</given-names></name><xref ref-type="aff" rid="Aff3">3</xref><xref ref-type="aff" rid="Aff4">4</xref></contrib><contrib contrib-type="author" corresp="yes"><name><surname>Malykhina</surname><given-names>Anna P.</given-names></name><address><email>Anna.Malykhina@ucdenver.edu</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2107 4242</institution-id><institution-id institution-id-type="GRID">grid.266100.3</institution-id><institution>Department of Urology,</institution><institution>University of California San Diego,</institution></institution-wrap>La Jolla, California USA</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Urology, Department of Surgery,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>Division of Endocrinology, Metabolism & Diabetes,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</aff><aff id="Aff4"><label>4</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0703 675X</institution-id><institution-id institution-id-type="GRID">grid.430503.1</institution-id><institution>NORC Metabolic and Cellular Analysis Core Center for Women’s Health Research,</institution><institution>University of Colorado Denver,</institution></institution-wrap>Aurora, Co USA</aff></contrib-group><pub-date pub-type="epub"><day>26</day><month>7</month><year>2019</year></pub-date><pub-date pub-type="pmc-release"><day>26</day><month>7</month><year>2019</year></pub-date><pub-date pub-type="collection"><year>2019</year></pub-date><volume>9</volume><elocation-id>10869</elocation-id><history><date date-type="received"><day>8</day><month>4</month><year>2019</year></date><date date-type="accepted"><day>16</day><month>7</month><year>2019</year></date></history><permissions><copyright-statement>© The Author(s) 2019</copyright-statement><license license-type="OpenAccess"><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Patients with multiple sclerosis (MS) develop a variety of lower urinary tract symptoms (LUTS). We previously characterized a murine model of neurogenic bladder dysfunction induced by a neurotropic strain of a coronavirus. In the present study, we further study the role of long-lasting neurodegeneration on the development of neurogenic bladder dysfunction in mice with corona-virus induced encephalitis (CIE). Long-term follow up study revealed three phenotypes of neurodegenerative symptom development: recovery (REC group), chronic progression (C-PRO group) and chronic disease with relapsing-remitting episodes (C-RELAP group). The levels of IL-1β in REC group, IL-10 in C-RELAP group, and IL-1β, IL-6, IL-10 and TNF-α in C-PRO group were diminished in the brain. The levels of TNF-α in REC group and INF-γ, IL-2, TGF-β and TNF-α in the C-PRO group were also diminished in the urinary bladder. Mice in C-RELAP group showed a delayed recovery of voiding function. <italic>In vitro</italic> contractility studies determined a decreased basal detrusor tone and reduced amplitude of nerve-mediated contractions in C-RELAP group, whereas C-PRO group had elevated muscle-mediated contractions. In conclusion, mice with CIE developed three phenotypes of neurologic impairment mimicking different types of MS progression in humans and showed differential mechanisms driving neurogenic bladder dysfunction.</p></abstract><kwd-group kwd-group-type="npg-subject"><title>Subject terms</title><kwd>Neurological disorders</kwd><kwd>Bladder</kwd></kwd-group><funding-group><award-group><funding-source><institution-wrap><institution-id institution-id-type="FundRef">https://doi.org/10.13039/100000062</institution-id><institution>U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)</institution></institution-wrap></funding-source><award-id>DK097819</award-id><principal-award-recipient><name><surname>Malykhina</surname><given-names>Anna P.</given-names></name></principal-award-recipient></award-group></funding-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© The Author(s) 2019</meta-value></custom-meta></custom-meta-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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