In Vivo Evidence for GABAA Receptor Changes in the Sensorimotor System in Primary Dystonia
Identifieur interne : 001B59 ( Main/Merge ); précédent : 001B58; suivant : 001B60In Vivo Evidence for GABAA Receptor Changes in the Sensorimotor System in Primary Dystonia
Auteurs : Valentina Garibotto [Italie] ; Luigi M. Romito [Italie] ; Antonio E. Elia [Italie] ; Paola Soliveri [Italie] ; Andrea Panzacchi [Italie] ; Assunta Carpinelli [Italie] ; Michele Tinazzi [Italie] ; Alberto Albanese [Italie] ; Daniela Perani [Italie]Source :
- Movement disorders [ 0885-3185 ] ; 2011.
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Abstract
Background: Preclinical and clinical evidence suggests that impaired gamma-aminobutyric (GABA) control, leading to disinhibition within the sensorimotor system, might play a role in dystonia. Aim of this study is the in vivo assessment of the GABAergic system in dystonia using positron emission tomography (PET) and 11C-flumazenil, a selective GABAA receptor ligand. Methods: Fourteen subjects with primary dystonia (9 carriers of the DYT1 mutation and 5 sporadic cases) were compared to 11 controls, using a simplified reference tissue model to measure binding potential. Results: Voxel-based analyses showed a reduction in GABAA receptor expression/affinity both in DYT1 carriers and sporadic patients in primary motor and premotor cortex, primary and secondary somatosensory cortex, and in the motor component of the cingulate gyrus. Conclusions: Dysfunction of GABAA receptors in sensorimotor systems in primary (genetic and sporadic) dystonia supports the view that lack of GABAergic control may be associated with the generation of dystonic movements.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">In Vivo Evidence for GABA<sub>A</sub> Receptor Changes in the Sensorimotor System in Primary Dystonia</title><author><name sortKey="Garibotto, Valentina" sort="Garibotto, Valentina" uniqKey="Garibotto V" first="Valentina" last="Garibotto">Valentina Garibotto</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Division of Neuroscience, Vita-Salute San Raffaele University</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Division of Neuroscience, San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Nuclear Medicine Unit, San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Romito, Luigi M" sort="Romito, Luigi M" uniqKey="Romito L" first="Luigi M." last="Romito">Luigi M. Romito</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology I, I.R.C.C.S. Istituto Neurologico "Carlo Besta"</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Neurology Institute, Università Cattolica del Sacro Cuore</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Elia, Antonio E" sort="Elia, Antonio E" uniqKey="Elia A" first="Antonio E." last="Elia">Antonio E. Elia</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology I, I.R.C.C.S. Istituto Neurologico "Carlo Besta"</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Neurology Institute, Università Cattolica del Sacro Cuore</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Soliveri, Paola" sort="Soliveri, Paola" uniqKey="Soliveri P" first="Paola" last="Soliveri">Paola Soliveri</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology I, I.R.C.C.S. Istituto Neurologico "Carlo Besta"</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Panzacchi, Andrea" sort="Panzacchi, Andrea" uniqKey="Panzacchi A" first="Andrea" last="Panzacchi">Andrea Panzacchi</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Division of Neuroscience, San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Nuclear Medicine Unit, San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Carpinelli, Assunta" sort="Carpinelli, Assunta" uniqKey="Carpinelli A" first="Assunta" last="Carpinelli">Assunta Carpinelli</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>IBFM-CNR</s1><s2>Milan</s2><s3>ITA</s3><sZ>6 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Tinazzi, Michele" sort="Tinazzi, Michele" uniqKey="Tinazzi M" first="Michele" last="Tinazzi">Michele Tinazzi</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurological and Visual Sciences, University of Verona</s1><s2>Verona</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Verona</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Neurology, Borgo Trento Hospital</s1><s2>Verona</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Verona</wicri:noRegion></affiliation></author><author><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology I, I.R.C.C.S. 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Romito</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology I, I.R.C.C.S. Istituto Neurologico "Carlo Besta"</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Neurology Institute, Università Cattolica del Sacro Cuore</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Elia, Antonio E" sort="Elia, Antonio E" uniqKey="Elia A" first="Antonio E." last="Elia">Antonio E. Elia</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology I, I.R.C.C.S. Istituto Neurologico "Carlo Besta"</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Neurology Institute, Università Cattolica del Sacro Cuore</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Soliveri, Paola" sort="Soliveri, Paola" uniqKey="Soliveri P" first="Paola" last="Soliveri">Paola Soliveri</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology I, I.R.C.C.S. Istituto Neurologico "Carlo Besta"</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Panzacchi, Andrea" sort="Panzacchi, Andrea" uniqKey="Panzacchi A" first="Andrea" last="Panzacchi">Andrea Panzacchi</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Division of Neuroscience, San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Nuclear Medicine Unit, San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Carpinelli, Assunta" sort="Carpinelli, Assunta" uniqKey="Carpinelli A" first="Assunta" last="Carpinelli">Assunta Carpinelli</name><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>IBFM-CNR</s1><s2>Milan</s2><s3>ITA</s3><sZ>6 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Tinazzi, Michele" sort="Tinazzi, Michele" uniqKey="Tinazzi M" first="Michele" last="Tinazzi">Michele Tinazzi</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Neurological and Visual Sciences, University of Verona</s1><s2>Verona</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Verona</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Neurology, Borgo Trento Hospital</s1><s2>Verona</s2><s3>ITA</s3><sZ>7 aut.</sZ></inist:fA14><country>Italie</country><wicri:noRegion>Verona</wicri:noRegion></affiliation></author><author><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology I, I.R.C.C.S. Istituto Neurologico "Carlo Besta"</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Neurology Institute, Università Cattolica del Sacro Cuore</s1><s2>Milan</s2><s3>ITA</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author><author><name sortKey="Perani, Daniela" sort="Perani, Daniela" uniqKey="Perani D" first="Daniela" last="Perani">Daniela Perani</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Division of Neuroscience, Vita-Salute San Raffaele University</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Division of Neuroscience, San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Nuclear Medicine Unit, San Raffaele Scientific Institute</s1><s2>Milan</s2><s3>ITA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Italie</country><placeName><settlement type="city">Milan</settlement><region nuts="2">Lombardie</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dystonia</term><term>Emission tomography</term><term>GABA</term><term>Gabaergic receptor A</term><term>Nervous system diseases</term><term>Positron emission tomography</term><term>Sensorimotor cortex</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Dystonie</term><term>Pathologie du système nerveux</term><term>Récepteur gabaergique A</term><term>GABA</term><term>Cortex sensorimoteur</term><term>Tomoscintigraphie</term><term>Tomographie par émission de positons</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Preclinical and clinical evidence suggests that impaired gamma-aminobutyric (GABA) control, leading to disinhibition within the sensorimotor system, might play a role in dystonia. Aim of this study is the in vivo assessment of the GABAergic system in dystonia using positron emission tomography (PET) and <sup>11</sup>C-flumazenil, a selective GABA<sub>A</sub> receptor ligand. Methods: Fourteen subjects with primary dystonia (9 carriers of the DYT1 mutation and 5 sporadic cases) were compared to 11 controls, using a simplified reference tissue model to measure binding potential. Results: Voxel-based analyses showed a reduction in GABA<sub>A</sub> receptor expression/affinity both in DYT1 carriers and sporadic patients in primary motor and premotor cortex, primary and secondary somatosensory cortex, and in the motor component of the cingulate gyrus. Conclusions: Dysfunction of GABA<sub>A</sub> receptors in sensorimotor systems in primary (genetic and sporadic) dystonia supports the view that lack of GABAergic control may be associated with the generation of dystonic movements.</div></front></TEI><affiliations><list><country><li>Italie</li></country><region><li>Lombardie</li></region><settlement><li>Milan</li></settlement></list><tree><country name="Italie"><region name="Lombardie"><name sortKey="Garibotto, Valentina" sort="Garibotto, Valentina" uniqKey="Garibotto V" first="Valentina" last="Garibotto">Valentina Garibotto</name></region><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><name sortKey="Albanese, Alberto" sort="Albanese, Alberto" uniqKey="Albanese A" first="Alberto" last="Albanese">Alberto Albanese</name><name sortKey="Carpinelli, Assunta" sort="Carpinelli, Assunta" uniqKey="Carpinelli A" first="Assunta" last="Carpinelli">Assunta Carpinelli</name><name sortKey="Elia, Antonio E" sort="Elia, Antonio E" uniqKey="Elia A" first="Antonio E." last="Elia">Antonio E. Elia</name><name sortKey="Elia, Antonio E" sort="Elia, Antonio E" uniqKey="Elia A" first="Antonio E." last="Elia">Antonio E. Elia</name><name sortKey="Garibotto, Valentina" sort="Garibotto, Valentina" uniqKey="Garibotto V" first="Valentina" last="Garibotto">Valentina Garibotto</name><name sortKey="Garibotto, Valentina" sort="Garibotto, Valentina" uniqKey="Garibotto V" first="Valentina" last="Garibotto">Valentina Garibotto</name><name sortKey="Panzacchi, Andrea" sort="Panzacchi, Andrea" uniqKey="Panzacchi A" first="Andrea" last="Panzacchi">Andrea Panzacchi</name><name sortKey="Panzacchi, Andrea" sort="Panzacchi, Andrea" uniqKey="Panzacchi A" first="Andrea" last="Panzacchi">Andrea Panzacchi</name><name sortKey="Perani, Daniela" sort="Perani, Daniela" uniqKey="Perani D" first="Daniela" last="Perani">Daniela Perani</name><name sortKey="Perani, Daniela" sort="Perani, Daniela" uniqKey="Perani D" first="Daniela" last="Perani">Daniela Perani</name><name sortKey="Perani, Daniela" sort="Perani, Daniela" uniqKey="Perani D" first="Daniela" last="Perani">Daniela Perani</name><name sortKey="Romito, Luigi M" sort="Romito, Luigi M" uniqKey="Romito L" first="Luigi M." last="Romito">Luigi M. Romito</name><name sortKey="Romito, Luigi M" sort="Romito, Luigi M" uniqKey="Romito L" first="Luigi M." last="Romito">Luigi M. Romito</name><name sortKey="Soliveri, Paola" sort="Soliveri, Paola" uniqKey="Soliveri P" first="Paola" last="Soliveri">Paola Soliveri</name><name sortKey="Tinazzi, Michele" sort="Tinazzi, Michele" uniqKey="Tinazzi M" first="Michele" last="Tinazzi">Michele Tinazzi</name><name sortKey="Tinazzi, Michele" sort="Tinazzi, Michele" uniqKey="Tinazzi M" first="Michele" last="Tinazzi">Michele Tinazzi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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