In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study
Identifieur interne : 000930 ( Pmc/Curation ); précédent : 000929; suivant : 000931In Vivo Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study
Auteurs : Tiing Yee Siow [Taïwan] ; Chiao-Chi V. Chen [Taïwan] ; Nina Wan [Canada] ; Kai-Ping N. Chow [Taïwan] ; Chen Chang [Taïwan]Source :
- BioMed Research International [ 2314-6133 ] ; 2013.
Abstract
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin commonly used to produce an animal model of Parkinson's disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO) synthase- (nNOS-) derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess
Url:
DOI: 10.1155/2013/964034
PubMed: 24069609
PubMed Central: 3773403
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>In Vivo</italic> Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study</title><author><name sortKey="Siow, Tiing Yee" sort="Siow, Tiing Yee" uniqKey="Siow T" first="Tiing Yee" last="Siow">Tiing Yee Siow</name><affiliation wicri:level="1"><nlm:aff id="I1">Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 33302, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 33302</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Chiao Chi V" sort="Chen, Chiao Chi V" uniqKey="Chen C" first="Chiao-Chi V." last="Chen">Chiao-Chi V. Chen</name><affiliation wicri:level="1"><nlm:aff id="I1">Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529</wicri:regionArea></affiliation></author><author><name sortKey="Wan, Nina" sort="Wan, Nina" uniqKey="Wan N" first="Nina" last="Wan">Nina Wan</name><affiliation wicri:level="1"><nlm:aff id="I3">School of Nursing, Queen's University, Kingston, ON, Canada K7L 3N6</nlm:aff><country>Canada</country><wicri:regionArea>School of Nursing, Queen's University, Kingston, ON</wicri:regionArea></affiliation></author><author><name sortKey="Chow, Kai Ping N" sort="Chow, Kai Ping N" uniqKey="Chow K" first="Kai-Ping N." last="Chow">Kai-Ping N. Chow</name><affiliation wicri:level="1"><nlm:aff id="I4">Department of Microbiology and Immunology, Chang-Gung University, Taoyuan 33302, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Microbiology and Immunology, Chang-Gung University, Taoyuan 33302</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Chen" sort="Chang, Chen" uniqKey="Chang C" first="Chen" last="Chang">Chen Chang</name><affiliation wicri:level="1"><nlm:aff id="I1">Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24069609</idno><idno type="pmc">3773403</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773403</idno><idno type="RBID">PMC:3773403</idno><idno type="doi">10.1155/2013/964034</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000930</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000930</idno><idno type="wicri:Area/Pmc/Curation">000930</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000930</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>In Vivo</italic> Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study</title><author><name sortKey="Siow, Tiing Yee" sort="Siow, Tiing Yee" uniqKey="Siow T" first="Tiing Yee" last="Siow">Tiing Yee Siow</name><affiliation wicri:level="1"><nlm:aff id="I1">Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="I2">Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 33302, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 33302</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Chiao Chi V" sort="Chen, Chiao Chi V" uniqKey="Chen C" first="Chiao-Chi V." last="Chen">Chiao-Chi V. Chen</name><affiliation wicri:level="1"><nlm:aff id="I1">Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529</wicri:regionArea></affiliation></author><author><name sortKey="Wan, Nina" sort="Wan, Nina" uniqKey="Wan N" first="Nina" last="Wan">Nina Wan</name><affiliation wicri:level="1"><nlm:aff id="I3">School of Nursing, Queen's University, Kingston, ON, Canada K7L 3N6</nlm:aff><country>Canada</country><wicri:regionArea>School of Nursing, Queen's University, Kingston, ON</wicri:regionArea></affiliation></author><author><name sortKey="Chow, Kai Ping N" sort="Chow, Kai Ping N" uniqKey="Chow K" first="Kai-Ping N." last="Chow">Kai-Ping N. Chow</name><affiliation wicri:level="1"><nlm:aff id="I4">Department of Microbiology and Immunology, Chang-Gung University, Taoyuan 33302, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Department of Microbiology and Immunology, Chang-Gung University, Taoyuan 33302</wicri:regionArea></affiliation></author><author><name sortKey="Chang, Chen" sort="Chang, Chen" uniqKey="Chang C" first="Chen" last="Chang">Chen Chang</name><affiliation wicri:level="1"><nlm:aff id="I1">Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan</nlm:aff><country xml:lang="fr">Taïwan</country><wicri:regionArea>Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529</wicri:regionArea></affiliation></author></analytic><series><title level="j">BioMed Research International</title><idno type="ISSN">2314-6133</idno><idno type="eISSN">2314-6141</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin commonly used to produce an animal model of Parkinson's disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO) synthase- (nNOS-) derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess <italic>in vivo</italic> due to its extremely short biological half-life, and so <italic>in vivo</italic> evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, <italic>in vivo</italic> localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI), intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF) in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first <italic>in vivo</italic> evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Biomed Res Int</journal-id><journal-id journal-id-type="iso-abbrev">Biomed Res Int</journal-id><journal-id journal-id-type="publisher-id">BMRI</journal-id><journal-title-group><journal-title>BioMed Research International</journal-title></journal-title-group><issn pub-type="ppub">2314-6133</issn><issn pub-type="epub">2314-6141</issn><publisher><publisher-name>Hindawi Publishing Corporation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24069609</article-id><article-id pub-id-type="pmc">3773403</article-id><article-id pub-id-type="doi">10.1155/2013/964034</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title><italic>In Vivo</italic> Evidence of Increased nNOS Activity in Acute MPTP Neurotoxicity: A Functional Pharmacological MRI Study</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Siow</surname><given-names>Tiing Yee</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref><xref ref-type="aff" rid="I2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chen</surname><given-names>Chiao-Chi V.</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Wan</surname><given-names>Nina</given-names></name><xref ref-type="aff" rid="I3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Chow</surname><given-names>Kai-Ping N.</given-names></name><xref ref-type="aff" rid="I4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0001-7152-3798</contrib-id><name><surname>Chang</surname><given-names>Chen</given-names></name><xref ref-type="aff" rid="I1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="I1"><sup>1</sup>Institute of Biomedical Sciences, Academia Sinica, 128 Section 2, Academia Road, Nankang, Taipei 11529, Taiwan</aff><aff id="I2"><sup>2</sup>Department of Medical Imaging and Intervention, Chang-Gung Memorial Hospital, Chang-Gung University College of Medicine, Taoyuan 33302, Taiwan</aff><aff id="I3"><sup>3</sup>School of Nursing, Queen's University, Kingston, ON, Canada K7L 3N6</aff><aff id="I4"><sup>4</sup>Department of Microbiology and Immunology, Chang-Gung University, Taoyuan 33302, Taiwan</aff><author-notes><corresp id="cor1">*Chen Chang: <email>bmcchen@ibms.sinica.edu.tw</email></corresp><fn fn-type="other"><p>Academic Editor: Tomio Inoue</p></fn></author-notes><pub-date pub-type="ppub"><year>2013</year></pub-date><pub-date pub-type="epub"><day>31</day><month>8</month><year>2013</year></pub-date><volume>2013</volume><elocation-id>964034</elocation-id><history><date date-type="received"><day>13</day><month>1</month><year>2013</year></date><date date-type="rev-recd"><day>21</day><month>7</month><year>2013</year></date><date date-type="accepted"><day>1</day><month>8</month><year>2013</year></date></history><permissions><copyright-statement>Copyright © 2013 Tiing Yee Siow et al.</copyright-statement><copyright-year>2013</copyright-year><license xlink:href="https://creativecommons.org/licenses/by/3.0/"><license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license></permissions><abstract><p>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin commonly used to produce an animal model of Parkinson's disease. Previous studies have suggested a critical role for neuronal nitric oxide (NO) synthase- (nNOS-) derived NO in the pathogenesis of MPTP. However, NO activity is difficult to assess <italic>in vivo</italic> due to its extremely short biological half-life, and so <italic>in vivo</italic> evidence of NO involvement in MPTP neurotoxicity remains scarce. In the present study, we utilized flow-sensitive alternating inversion recovery sequences, <italic>in vivo</italic> localized proton magnetic resonance spectroscopy, and diffusion-weighted imaging to, respectively, assess the hemodynamics, metabolism, and cytotoxicity induced by MPTP. The role of NO in MPTP toxicity was clarified further by administering a selective nNOS inhibitor, 7-nitroindazole (7-NI), intraperitoneally to some of the experimental animals prior to MPTP challenge. The transient increase in cerebral blood flow (CBF) in the cortex and striatum induced by systemic injection of MPTP was completely prevented by pretreatment with 7-NI. We provide the first <italic>in vivo</italic> evidence of increased nNOS activity in acute MPTP-induced neurotoxicity. Although the observed CBF change may be independent of the toxicogenesis of MPTP, this transient hyperperfusion state may serve as an early indicator of neuroinflammation.</p></abstract></article-meta></front><floats-group><fig id="fig1" orientation="portrait" position="float"><label>Figure 1</label><caption><p>Temporal FAIR images. Representative temporal FAIR images from (a) an MPTP-treated rat, (b) a 7-NI-pretreated and MPTP-treated rat, and (c) a saline-treated (control) rat at baseline (ctrl) and various times postinjection. Progressive elevations of CBF were observed in the cortex and striatum of rats treated with MPTP alone. These elevations were prevented by pretreatment with 7-NI. There were essentially no changes in CBF in either brain region over time in the control rats.</p></caption><graphic xlink:href="BMRI2013-964034.001"></graphic></fig><fig id="fig2" orientation="portrait" position="float"><label>Figure 2</label><caption><p>CBF changes over time. Temporal changes in CBF in the cortical and striatal regions of saline-treated (control (Cont)) and MPTP-treated rats. Pretreatment with 7-NI prevented the elevation of CBF induced by MPTP. Data are mean and SD values.</p></caption><graphic xlink:href="BMRI2013-964034.002"></graphic></fig></floats-group></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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