NEUROCHEMICAL ALTERATIONS IN SPINOCEREBELLAR ATAXIA TYPE 1 AND THEIR CORRELATIONS WITH CLINICAL STATUS
Identifieur interne : 000326 ( Pmc/Checkpoint ); précédent : 000325; suivant : 000327NEUROCHEMICAL ALTERATIONS IN SPINOCEREBELLAR ATAXIA TYPE 1 AND THEIR CORRELATIONS WITH CLINICAL STATUS
Auteurs : Gülin Öz [États-Unis] ; Diane Hutter [États-Unis] ; Ivan Tká [États-Unis] ; H. Brent Clark [États-Unis] ; Myron D. Gross [États-Unis] ; Hong Jiang [États-Unis] ; Lynn E. Eberly [États-Unis] ; Khalaf O. Bushara [États-Unis] ; Christopher M. Gomez [États-Unis]Source :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2010.
Abstract
Robust biomarkers of neurodegeneration are critical for testing of neuroprotective therapies. The clinical applicability of such biomarkers requires sufficient sensitivity to detect disease in individuals. Here we tested the sensitivity of high field (4 tesla) proton magnetic resonance spectroscopy (1H MRS) to neurochemical alterations in the cerebellum and brainstem in spinocerebellar ataxia type 1 (SCA1). We measured neurochemical profiles that consisted of 10–15 metabolite concentrations in the vermis, cerebellar hemispheres and pons of patients with SCA1 (N=9) and healthy controls (N=15). Total NAA (N-acetylaspartate + N-acetylaspartylglutamate, tNAA) and glutamate were lower and glutamine,
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DOI: 10.1002/mds.23067
PubMed: 20310029
PubMed Central: 2916651
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Brent" last="Clark">H. Brent Clark</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Gross, Myron D" sort="Gross, Myron D" uniqKey="Gross M" first="Myron D." last="Gross">Myron D. Gross</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Jiang, Hong" sort="Jiang, Hong" uniqKey="Jiang H" first="Hong" last="Jiang">Hong Jiang</name><affiliation wicri:level="2"><nlm:aff id="A3">Visiting scientist, Department of Neurology, University of Chicago, Chicago, IL, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Visiting scientist, Department of Neurology, University of Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Eberly, Lynn E" sort="Eberly, Lynn E" uniqKey="Eberly L" first="Lynn E." last="Eberly">Lynn E. 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Bushara</name><affiliation wicri:level="2"><nlm:aff id="A5">Department of Neurology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Gomez, Christopher M" sort="Gomez, Christopher M" uniqKey="Gomez C" first="Christopher M." last="Gomez">Christopher M. Gomez</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Neurology, University of Chicago, Chicago, IL, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">20310029</idno><idno type="pmc">2916651</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916651</idno><idno type="RBID">PMC:2916651</idno><idno type="doi">10.1002/mds.23067</idno><date when="2010">2010</date><idno type="wicri:Area/Pmc/Corpus">000086</idno><idno type="wicri:Area/Pmc/Curation">000086</idno><idno type="wicri:Area/Pmc/Checkpoint">000326</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">NEUROCHEMICAL ALTERATIONS IN SPINOCEREBELLAR ATAXIA TYPE 1 AND THEIR CORRELATIONS WITH CLINICAL STATUS</title><author><name sortKey="Oz, Gulin" sort="Oz, Gulin" uniqKey="Oz G" first="Gülin" last="Öz">Gülin Öz</name><affiliation wicri:level="2"><nlm:aff id="A1">Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Hutter, Diane" sort="Hutter, Diane" uniqKey="Hutter D" first="Diane" last="Hutter">Diane Hutter</name><affiliation wicri:level="2"><nlm:aff id="A1">Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Tka, Ivan" sort="Tka, Ivan" uniqKey="Tka I" first="Ivan" last="Tká">Ivan Tká</name><affiliation wicri:level="2"><nlm:aff id="A1">Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Clark, H Brent" sort="Clark, H Brent" uniqKey="Clark H" first="H. Brent" last="Clark">H. Brent Clark</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Gross, Myron D" sort="Gross, Myron D" uniqKey="Gross M" first="Myron D." last="Gross">Myron D. Gross</name><affiliation wicri:level="2"><nlm:aff id="A2">Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Jiang, Hong" sort="Jiang, Hong" uniqKey="Jiang H" first="Hong" last="Jiang">Hong Jiang</name><affiliation wicri:level="2"><nlm:aff id="A3">Visiting scientist, Department of Neurology, University of Chicago, Chicago, IL, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Visiting scientist, Department of Neurology, University of Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author><author><name sortKey="Eberly, Lynn E" sort="Eberly, Lynn E" uniqKey="Eberly L" first="Lynn E." last="Eberly">Lynn E. Eberly</name><affiliation wicri:level="2"><nlm:aff id="A4">Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Bushara, Khalaf O" sort="Bushara, Khalaf O" uniqKey="Bushara K" first="Khalaf O." last="Bushara">Khalaf O. Bushara</name><affiliation wicri:level="2"><nlm:aff id="A5">Department of Neurology, Medical School, University of Minnesota, Minneapolis, MN, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, Medical School, University of Minnesota, Minneapolis, MN</wicri:regionArea><placeName><region type="state">Minnesota</region></placeName></affiliation></author><author><name sortKey="Gomez, Christopher M" sort="Gomez, Christopher M" uniqKey="Gomez C" first="Christopher M." last="Gomez">Christopher M. Gomez</name><affiliation wicri:level="2"><nlm:aff id="A6">Department of Neurology, University of Chicago, Chicago, IL, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Neurology, University of Chicago, Chicago, IL</wicri:regionArea><placeName><region type="state">Illinois</region></placeName></affiliation></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><idno type="eISSN">1531-8257</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P2">Robust biomarkers of neurodegeneration are critical for testing of neuroprotective therapies. The clinical applicability of such biomarkers requires sufficient sensitivity to detect disease in individuals. Here we tested the sensitivity of high field (4 tesla) proton magnetic resonance spectroscopy (<sup>1</sup>H MRS) to neurochemical alterations in the cerebellum and brainstem in spinocerebellar ataxia type 1 (SCA1). We measured neurochemical profiles that consisted of 10–15 metabolite concentrations in the vermis, cerebellar hemispheres and pons of patients with SCA1 (N=9) and healthy controls (N=15). Total NAA (N-acetylaspartate + N-acetylaspartylglutamate, tNAA) and glutamate were lower and glutamine, <italic>myo</italic>-inositol and total creatine (creatine + phosphocreatine, tCr) were higher in patients relative to controls, consistent with neuronal dysfunction/loss, gliotic activity and alterations in glutamate-glutamine cycling and energy metabolism. Changes in tNAA, tCr, <italic>myo</italic>-inositol and glutamate levels were discernible in individual spectra and the tNAA/<italic>myo</italic>-inositol ratio in the cerebellar hemipheres and pons differentiated the patients from controls with 100% specificity and sensitivity. In addition, tNAA, <italic>myo</italic>-inositol and glutamate levels in the cerebellar hemispheres and the tNAA and <italic>myo</italic>-inositol levels in the pons correlated with ataxia scores (Scale for the Assessment and Rating of Ataxia, SARA). Two other biomarkers measured in the cerebrospinal fluid (CSF) of a subset of the volunteers (F<sub>2</sub>-isoprostanes as a marker of oxidative stress and glial fibrillary acidic protein (GFAP) as a marker of gliosis) were not different between patients and controls. These data demonstrate that <sup>1</sup>H MRS biomarkers can be utilized to non-invasively assess neuronal and glial status in individual ataxia patients.</p></div></front></TEI><pmc article-type="research-article" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8610688</journal-id><journal-id journal-id-type="pubmed-jr-id">5937</journal-id><journal-id journal-id-type="nlm-ta">Mov Disord</journal-id><journal-title>Movement disorders : official journal of the Movement Disorder Society</journal-title><issn pub-type="ppub">0885-3185</issn><issn pub-type="epub">1531-8257</issn></journal-meta><article-meta><article-id pub-id-type="pmid">20310029</article-id><article-id pub-id-type="pmc">2916651</article-id><article-id pub-id-type="doi">10.1002/mds.23067</article-id><article-id pub-id-type="manuscript">NIHMS216543</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>NEUROCHEMICAL ALTERATIONS IN SPINOCEREBELLAR ATAXIA TYPE 1 AND THEIR CORRELATIONS WITH CLINICAL STATUS</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Öz</surname><given-names>Gülin</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hutter</surname><given-names>Diane</given-names></name><degrees>RN</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Tkáč</surname><given-names>Ivan</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Clark</surname><given-names>H. Brent</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Gross</surname><given-names>Myron D.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Jiang</surname><given-names>Hong</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Eberly</surname><given-names>Lynn E.</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Bushara</surname><given-names>Khalaf O.</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A5">5</xref></contrib><contrib contrib-type="author"><name><surname>Gomez</surname><given-names>Christopher M.</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A6">6</xref></contrib></contrib-group><aff id="A1"><label>1</label>Center for MR Research, Department of Radiology, Medical School, University of Minnesota, Minneapolis, MN, USA</aff><aff id="A2"><label>2</label>Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, MN, USA</aff><aff id="A3"><label>3</label>Visiting scientist, Department of Neurology, University of Chicago, Chicago, IL, USA</aff><aff id="A4"><label>4</label>Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA</aff><aff id="A5"><label>5</label>Department of Neurology, Medical School, University of Minnesota, Minneapolis, MN, USA</aff><aff id="A6"><label>6</label>Department of Neurology, University of Chicago, Chicago, IL, USA</aff><author-notes><corresp id="cor1">Correspondence to: Gülin Öz, Center for MR Research, 2021 6<sup>th</sup> St. S.E., Minneapolis, MN 55455, Tel: +1 612 625-7897, Fax: +1 612 626-2004, <email>gulin@cmrr.umn.edu</email></corresp><fn id="FN1" fn-type="present-address"><p id="P1">Present address for Hong Jiang: Department of Neurology, Xiangya Hospital Neurodegenerative Disorders Research Center, Central South University, Changsha, Hunan, P.R.China</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>30</day><month>6</month><year>2010</year></pub-date><pub-date pub-type="ppub"><day>15</day><month>7</month><year>2010</year></pub-date><pub-date pub-type="pmc-release"><day>15</day><month>7</month><year>2011</year></pub-date><volume>25</volume><issue>9</issue><fpage>1253</fpage><lpage>1261</lpage><abstract><p id="P2">Robust biomarkers of neurodegeneration are critical for testing of neuroprotective therapies. The clinical applicability of such biomarkers requires sufficient sensitivity to detect disease in individuals. Here we tested the sensitivity of high field (4 tesla) proton magnetic resonance spectroscopy (<sup>1</sup>H MRS) to neurochemical alterations in the cerebellum and brainstem in spinocerebellar ataxia type 1 (SCA1). We measured neurochemical profiles that consisted of 10–15 metabolite concentrations in the vermis, cerebellar hemispheres and pons of patients with SCA1 (N=9) and healthy controls (N=15). Total NAA (N-acetylaspartate + N-acetylaspartylglutamate, tNAA) and glutamate were lower and glutamine, <italic>myo</italic>-inositol and total creatine (creatine + phosphocreatine, tCr) were higher in patients relative to controls, consistent with neuronal dysfunction/loss, gliotic activity and alterations in glutamate-glutamine cycling and energy metabolism. Changes in tNAA, tCr, <italic>myo</italic>-inositol and glutamate levels were discernible in individual spectra and the tNAA/<italic>myo</italic>-inositol ratio in the cerebellar hemipheres and pons differentiated the patients from controls with 100% specificity and sensitivity. In addition, tNAA, <italic>myo</italic>-inositol and glutamate levels in the cerebellar hemispheres and the tNAA and <italic>myo</italic>-inositol levels in the pons correlated with ataxia scores (Scale for the Assessment and Rating of Ataxia, SARA). Two other biomarkers measured in the cerebrospinal fluid (CSF) of a subset of the volunteers (F<sub>2</sub>-isoprostanes as a marker of oxidative stress and glial fibrillary acidic protein (GFAP) as a marker of gliosis) were not different between patients and controls. These data demonstrate that <sup>1</sup>H MRS biomarkers can be utilized to non-invasively assess neuronal and glial status in individual ataxia patients.</p></abstract><kwd-group><kwd>SCA1</kwd><kwd>MRS</kwd><kwd>ataxia</kwd><kwd>cerebellum</kwd><kwd>neurochemical profile</kwd></kwd-group><contract-num rid="NS1">P30 NS057091-04
||NS</contract-num><contract-sponsor id="NS1">National Institute of Neurological Disorders and Stroke : NINDS</contract-sponsor></article-meta></front></pmc><affiliations><list><country><li>États-Unis</li></country><region><li>Illinois</li><li>Minnesota</li></region></list><tree><country name="États-Unis"><region name="Minnesota"><name sortKey="Oz, Gulin" sort="Oz, Gulin" uniqKey="Oz G" first="Gülin" last="Öz">Gülin Öz</name></region><name sortKey="Bushara, Khalaf O" sort="Bushara, Khalaf O" uniqKey="Bushara K" first="Khalaf O." last="Bushara">Khalaf O. Bushara</name><name sortKey="Clark, H Brent" sort="Clark, H Brent" uniqKey="Clark H" first="H. Brent" last="Clark">H. Brent Clark</name><name sortKey="Eberly, Lynn E" sort="Eberly, Lynn E" uniqKey="Eberly L" first="Lynn E." last="Eberly">Lynn E. Eberly</name><name sortKey="Gomez, Christopher M" sort="Gomez, Christopher M" uniqKey="Gomez C" first="Christopher M." last="Gomez">Christopher M. Gomez</name><name sortKey="Gross, Myron D" sort="Gross, Myron D" uniqKey="Gross M" first="Myron D." last="Gross">Myron D. Gross</name><name sortKey="Hutter, Diane" sort="Hutter, Diane" uniqKey="Hutter D" first="Diane" last="Hutter">Diane Hutter</name><name sortKey="Jiang, Hong" sort="Jiang, Hong" uniqKey="Jiang H" first="Hong" last="Jiang">Hong Jiang</name><name sortKey="Tka, Ivan" sort="Tka, Ivan" uniqKey="Tka I" first="Ivan" last="Tká">Ivan Tká</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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