Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum
Identifieur interne : 001729 ( PascalFrancis/Checkpoint ); précédent : 001728; suivant : 001730Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum
Auteurs : M.-T. Herrero [Espagne] ; S. J. Augood ; E. C. Hirsch [France] ; F. Javoy-Agid [France] ; M. R. Luquin [Espagne] ; Yves Agid [France] ; J. A. Obeso [Espagne] ; P. C. EmsonSource :
- Neuroscience [ 0306-4522 ] ; 1995.
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Abstract
The cellular expression of the genes encoding the neuropeptides enkephalin and substance P were examined in the caudate nucleus and putamen of parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys by in situ hybridization using radioactive antisense oligonucleotides coupled with computer-assisted image analysis. Behavioural evaluation of the animals revealed two levels of motor impairment ; one group moderately impaired and the other severely disabled. A marked increase in the cellular content of preproenkephalin A messenger RNA was observed in medium-sized (106±9 μm2) cells in the caudate-putamen of all MPTP animals when compared with controls, the increase being greatest in the most severely impaired animals. By contrast, a marked reduction in the cellular abundance of preprotachykinin gene expression was detected in striatal cells (101±16 μm2) of these same MPTP animals. These changes in neuropeptide gene expression were not associated with a change in the density (approximately 10 cells per mm2) of messenger RNA-expressing cells. L-DOPA treatment of two of the severely-impaired MPTP monkeys resulted in a dissociation of expression of these two genes : the cellular abundance of preproenkephalin A remained elevated whilst preprotachykinin levels were normalized and comparable with controls. No change in the cellular abundance of preprotachykinin messenger RNA was observed in cells of the insular cortex or a small discrete population of large cells (208 ± 27 μm2) in the ventral putamen. These results demonstrate that MPTP treatment of primates results in a marked potentiation in preproenkephalin messenger RNA coupled with an attenuation in preprotachykinin messenger RNA in the dopamine-denervated caudate-putamen. L-DOPA therapy given on an intermittent schedule reverses the decrease in preprotachykinin messenger RNA, but fails to reverse the increase in preproenkephalin messenger RNA in the same animal. These observations suggest that a dissociation of the activity of these two neuropeptide systems may underlie the improvement in motor skill that accompanies dopamine replacement therapy and that this dissociation may well be instrumental in the long-term complications associated with L-DOPA therapy.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum</title><author><name sortKey="Herrero, M T" sort="Herrero, M T" uniqKey="Herrero M" first="M.-T." last="Herrero">M.-T. Herrero</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Univ. Navarra, clín. univ., neurologia exp.</s1><s2>31080 Pamplona</s2><s3>ESP</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Espagne</country><placeName><region nuts="2" type="communauté">Communauté forale de Navarre</region></placeName></affiliation></author><author><name sortKey="Augood, S J" sort="Augood, S J" uniqKey="Augood S" first="S. J." last="Augood">S. J. Augood</name></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E. C." last="Hirsch">E. C. Hirsch</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>INSERM Hôp. Salpêtrière, U289</s1><s2>75651 Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Javoy Agid, F" sort="Javoy Agid, F" uniqKey="Javoy Agid F" first="F." last="Javoy-Agid">F. Javoy-Agid</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>INSERM Hôp. Salpêtrière, U289</s1><s2>75651 Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Luquin, M R" sort="Luquin, M R" uniqKey="Luquin M" first="M. R." last="Luquin">M. R. Luquin</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Univ. Navarra, clín. univ., neurologia exp.</s1><s2>31080 Pamplona</s2><s3>ESP</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Espagne</country><placeName><region nuts="2" type="communauté">Communauté forale de Navarre</region></placeName></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Yves Agid</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>INSERM Hôp. Salpêtrière, U289</s1><s2>75651 Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author><author><name sortKey="Obeso, J A" sort="Obeso, J A" uniqKey="Obeso J" first="J. A." last="Obeso">J. A. Obeso</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Univ. Navarra, clín. univ., neurologia exp.</s1><s2>31080 Pamplona</s2><s3>ESP</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Espagne</country><placeName><region nuts="2" type="communauté">Communauté forale de Navarre</region></placeName></affiliation></author><author><name sortKey="Emson, P C" sort="Emson, P C" uniqKey="Emson P" first="P. C." last="Emson">P. C. Emson</name></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">95-0514048</idno><date when="1995">1995</date><idno type="stanalyst">PASCAL 95-0514048 INIST</idno><idno type="RBID">Pascal:95-0514048</idno><idno type="wicri:Area/PascalFrancis/Corpus">001864</idno><idno type="wicri:Area/PascalFrancis/Curation">001783</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">001729</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">001729</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum</title><author><name sortKey="Herrero, M T" sort="Herrero, M T" uniqKey="Herrero M" first="M.-T." last="Herrero">M.-T. Herrero</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Univ. Navarra, clín. univ., neurologia exp.</s1><s2>31080 Pamplona</s2><s3>ESP</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Espagne</country><placeName><region nuts="2" type="communauté">Communauté forale de Navarre</region></placeName></affiliation></author><author><name sortKey="Augood, S J" sort="Augood, S J" uniqKey="Augood S" first="S. J." last="Augood">S. J. Augood</name></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E. C." last="Hirsch">E. C. Hirsch</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>INSERM Hôp. Salpêtrière, U289</s1><s2>75651 Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Javoy Agid, F" sort="Javoy Agid, F" uniqKey="Javoy Agid F" first="F." last="Javoy-Agid">F. Javoy-Agid</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>INSERM Hôp. Salpêtrière, U289</s1><s2>75651 Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Luquin, M R" sort="Luquin, M R" uniqKey="Luquin M" first="M. R." last="Luquin">M. R. Luquin</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Univ. Navarra, clín. univ., neurologia exp.</s1><s2>31080 Pamplona</s2><s3>ESP</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Espagne</country><placeName><region nuts="2" type="communauté">Communauté forale de Navarre</region></placeName></affiliation></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Yves Agid</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>INSERM Hôp. Salpêtrière, U289</s1><s2>75651 Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author><author><name sortKey="Obeso, J A" sort="Obeso, J A" uniqKey="Obeso J" first="J. A." last="Obeso">J. A. Obeso</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Univ. Navarra, clín. univ., neurologia exp.</s1><s2>31080 Pamplona</s2><s3>ESP</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Espagne</country><placeName><region nuts="2" type="communauté">Communauté forale de Navarre</region></placeName></affiliation></author><author><name sortKey="Emson, P C" sort="Emson, P C" uniqKey="Emson P" first="P. C." last="Emson">P. C. Emson</name></author></analytic><series><title level="j" type="main">Neuroscience</title><title level="j" type="abbreviated">Neuroscience</title><idno type="ISSN">0306-4522</idno><imprint><date when="1995">1995</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Neuroscience</title><title level="j" type="abbreviated">Neuroscience</title><idno type="ISSN">0306-4522</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term><term>Antiparkinson agent</term><term>Corpus striatum</term><term>Dopa</term><term>Experimental disease</term><term>Gene expression</term><term>Monkey</term><term>Neurotoxin</term><term>Parkinson disease</term><term>Preproenkephalin</term><term>Tachykinin</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Dopa</term><term>Préproenképhaline</term><term>Tachykinine</term><term>Neurotoxine</term><term>Corps strié</term><term>Expression génique</term><term>Antiparkinsonien</term><term>Traitement</term><term>Parkinson maladie</term><term>Animal</term><term>Pathologie expérimentale</term><term>Singe</term><term>MPTP</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Singe</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The cellular expression of the genes encoding the neuropeptides enkephalin and substance P were examined in the caudate nucleus and putamen of parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys by in situ hybridization using radioactive antisense oligonucleotides coupled with computer-assisted image analysis. Behavioural evaluation of the animals revealed two levels of motor impairment ; one group moderately impaired and the other severely disabled. A marked increase in the cellular content of preproenkephalin A messenger RNA was observed in medium-sized (106±9 μm<sup>2</sup>) cells in the caudate-putamen of all MPTP animals when compared with controls, the increase being greatest in the most severely impaired animals. By contrast, a marked reduction in the cellular abundance of preprotachykinin gene expression was detected in striatal cells (101±16 μm<sup>2</sup>) of these same MPTP animals. These changes in neuropeptide gene expression were not associated with a change in the density (approximately 10 cells per mm<sup>2</sup>) of messenger RNA-expressing cells. L-DOPA treatment of two of the severely-impaired MPTP monkeys resulted in a dissociation of expression of these two genes : the cellular abundance of preproenkephalin A remained elevated whilst preprotachykinin levels were normalized and comparable with controls. No change in the cellular abundance of preprotachykinin messenger RNA was observed in cells of the insular cortex or a small discrete population of large cells (208 ± 27 μm<sup>2</sup>) in the ventral putamen. These results demonstrate that MPTP treatment of primates results in a marked potentiation in preproenkephalin messenger RNA coupled with an attenuation in preprotachykinin messenger RNA in the dopamine-denervated caudate-putamen. L-DOPA therapy given on an intermittent schedule reverses the decrease in preprotachykinin messenger RNA, but fails to reverse the increase in preproenkephalin messenger RNA in the same animal. These observations suggest that a dissociation of the activity of these two neuropeptide systems may underlie the improvement in motor skill that accompanies dopamine replacement therapy and that this dissociation may well be instrumental in the long-term complications associated with L-DOPA therapy.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0306-4522</s0></fA01><fA02 i1="01"><s0>NRSCDN</s0></fA02><fA03 i2="1"><s0>Neuroscience</s0></fA03><fA05><s2>68</s2></fA05><fA06><s2>4</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Effects of L-DOPA on preproenkephalin and preprotackykinin gene expression in the MPTP-treated monkey striatum</s1></fA08><fA11 i1="01" i2="1"><s1>HERRERO (M.-T.)</s1></fA11><fA11 i1="02" i2="1"><s1>AUGOOD (S. J.)</s1></fA11><fA11 i1="03" i2="1"><s1>HIRSCH (E. C.)</s1></fA11><fA11 i1="04" i2="1"><s1>JAVOY-AGID (F.)</s1></fA11><fA11 i1="05" i2="1"><s1>LUQUIN (M. R.)</s1></fA11><fA11 i1="06" i2="1"><s1>AGID (Y.)</s1></fA11><fA11 i1="07" i2="1"><s1>OBESO (J. A.)</s1></fA11><fA11 i1="08" i2="1"><s1>EMSON (P. C.)</s1></fA11><fA14 i1="01"><s1>Univ. Navarra, clín. univ., neurologia exp.</s1><s2>31080 Pamplona</s2><s3>ESP</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></fA14><fA14 i1="02"><s1>INSERM Hôp. Salpêtrière, U289</s1><s2>75651 Paris</s2><s3>FRA</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>6 aut.</sZ></fA14><fA20><s1>1189-1198</s1></fA20><fA21><s1>1995</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>17194</s2><s5>354000054624040200</s5></fA43><fA44><s0>0000</s0></fA44><fA45><s0>60 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>95-0514048</s0></fA47><fA60><s1>P</s1><s3>PR</s3></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Neuroscience</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>The cellular expression of the genes encoding the neuropeptides enkephalin and substance P were examined in the caudate nucleus and putamen of parkinsonian 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated cynomolgus monkeys by in situ hybridization using radioactive antisense oligonucleotides coupled with computer-assisted image analysis. Behavioural evaluation of the animals revealed two levels of motor impairment ; one group moderately impaired and the other severely disabled. A marked increase in the cellular content of preproenkephalin A messenger RNA was observed in medium-sized (106±9 μm<sup>2</sup>) cells in the caudate-putamen of all MPTP animals when compared with controls, the increase being greatest in the most severely impaired animals. By contrast, a marked reduction in the cellular abundance of preprotachykinin gene expression was detected in striatal cells (101±16 μm<sup>2</sup>) of these same MPTP animals. These changes in neuropeptide gene expression were not associated with a change in the density (approximately 10 cells per mm<sup>2</sup>) of messenger RNA-expressing cells. L-DOPA treatment of two of the severely-impaired MPTP monkeys resulted in a dissociation of expression of these two genes : the cellular abundance of preproenkephalin A remained elevated whilst preprotachykinin levels were normalized and comparable with controls. No change in the cellular abundance of preprotachykinin messenger RNA was observed in cells of the insular cortex or a small discrete population of large cells (208 ± 27 μm<sup>2</sup>) in the ventral putamen. These results demonstrate that MPTP treatment of primates results in a marked potentiation in preproenkephalin messenger RNA coupled with an attenuation in preprotachykinin messenger RNA in the dopamine-denervated caudate-putamen. L-DOPA therapy given on an intermittent schedule reverses the decrease in preprotachykinin messenger RNA, but fails to reverse the increase in preproenkephalin messenger RNA in the same animal. These observations suggest that a dissociation of the activity of these two neuropeptide systems may underlie the improvement in motor skill that accompanies dopamine replacement therapy and that this dissociation may well be instrumental in the long-term complications associated with L-DOPA therapy.</s0></fC01><fC02 i1="01" i2="X"><s0>002B02B06</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Dopa</s0><s2>NK</s2><s2>FR</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Dopa</s0><s2>NK</s2><s2>FR</s2><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Dopa</s0><s2>NK</s2><s2>FR</s2><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Préproenképhaline</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Preproenkephalin</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Preproencefalina</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Tachykinine</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Tachykinin</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" 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patología</s0><s5>38</s5></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Système nerveux central pathologie</s0><s5>39</s5></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0><s5>39</s5></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0><s5>39</s5></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Encéphale pathologie</s0><s5>40</s5></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Cerebral disorder</s0><s5>40</s5></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Encéfalo patología</s0><s5>40</s5></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Extrapyramidal syndrome</s0><s5>41</s5></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0><s5>41</s5></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0><s5>41</s5></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Maladie dégénérative</s0><s5>42</s5></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Degenerative disease</s0><s5>42</s5></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0><s5>42</s5></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Primates</s0><s2>NS</s2></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Primates</s0><s2>NS</s2></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Primates</s0><s2>NS</s2></fC07><fC07 i1="10" i2="X" l="FRE"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="10" i2="X" l="ENG"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="10" i2="X" l="SPA"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="11" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="11" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="11" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fN21><s1>289</s1></fN21></pA></standard></inist><affiliations><list><country><li>Espagne</li><li>France</li></country><region><li>Communauté forale de Navarre</li><li>Île-de-France</li></region><settlement><li>Paris</li></settlement><orgName><li>Hôpital de la Salpêtrière</li></orgName></list><tree><noCountry><name sortKey="Augood, S J" sort="Augood, S J" uniqKey="Augood S" first="S. J." last="Augood">S. J. Augood</name><name sortKey="Emson, P C" sort="Emson, P C" uniqKey="Emson P" first="P. C." last="Emson">P. C. Emson</name></noCountry><country name="Espagne"><region name="Communauté forale de Navarre"><name sortKey="Herrero, M T" sort="Herrero, M T" uniqKey="Herrero M" first="M.-T." last="Herrero">M.-T. Herrero</name></region><name sortKey="Luquin, M R" sort="Luquin, M R" uniqKey="Luquin M" first="M. R." last="Luquin">M. R. Luquin</name><name sortKey="Obeso, J A" sort="Obeso, J A" uniqKey="Obeso J" first="J. A." last="Obeso">J. A. Obeso</name></country><country name="France"><region name="Île-de-France"><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E. C." last="Hirsch">E. C. Hirsch</name></region><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y." last="Agid">Yves Agid</name><name sortKey="Javoy Agid, F" sort="Javoy Agid, F" uniqKey="Javoy Agid F" first="F." last="Javoy-Agid">F. Javoy-Agid</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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