Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys
Identifieur interne : 000420 ( Main/Corpus ); précédent : 000419; suivant : 000421Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys
Auteurs : Jane R. Taylor ; John D. Elsworth ; John R. Sladek Jr. ; Timothy J. Collier ; Robert H. Roth ; D. Eugene Redmond Jr.Source :
- Cell Transplantation [ 0963-6897 ] ; 1994.
Abstract
Parkinsonism has been reported to improve following transplantation of fetal mesencephalic tissue into the striatum of MPTP-exposed monkeys and humans and in patients with idiopathic Parkinson's disease. While there is good evidence for the survival of grafted tyrosine hydroxy-lase (TH)-positive cells in animal studies, it is not known whether they produce neuronal effects that account for behavioral improvement after transplantation or whether spontaneous or graft-induced changes in the host striatum are at least partly responsible. Are neuronal synaptic connections and dopamine release necessary, or would “toenails and talcum powder” do the job equally well? We have addressed these questions by studying several types of implantation surgeries, including sham surgery, the implantation of cerebellar tissue, and the implantation of mesencephalic TH-positive fetal tissue of various gestational ages into the striatum. Adult male African green monkeys received systemic MPTP administration (cumulative doses of 2.0–2.5 mg/kg) prior to these stereotaxic surgical manipulations. Subjects were matched for quantitative behavioral deficits prior to surgery. Subjects were examined and assessments made by “blinded” observers who scored individual spontaneous and elicited behaviors. Observers were trained and tested repeatedly for inter-rater reliability. A “parkinsonian summary score” derived and determined using a principal component factor analysis of a large sample of data from MPTP-treated and normal monkeys of the same species was used to assess behavior. Postmortem brain tissue was prepared for biochemical analysis of dopamine concentrations and TH immunohistochemical studies. The most dramatic improvement was seen in monkeys with “early” (<4 cm fetal crown rump length) surviving substantia nigra grafts in the caudate nucleus. Some behavioral improvements were seen in MPTP-treated sham-operated monkeys, cerebellar-grafted monkeys, and “later” (>14 cm fetal crown rump length) substantia nigra-grafted monkeys. These changes in monkeys which did not have surviving dopamine-producing grafts probably represent the recovery capacity of MPTP-treated host brain during this time interval since un-operated subjects showed similar changes. More variable effects were seen with substantia nigra grafts in the putamen. The most consistent correlate of behavioral improvement in all experimental groups was elevation in dopamine concentrations near the grafts compared with a distant striatal location which is believed to represent the depletion without the effects of the grafts. While these data do not establish the precise mechanism of action, they point to a hierarchy of factors which provide increasingly larger restorative effects, including sprouting of host neurons and increased dopamine production by grafted fetal dopamine neurons. Sham surgery appears to be significantly less effective than early fetal mesencephalic tissue which survives and releases dopamine.
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DOI: 10.1016/0963-6897(94)00035-I
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys</title><author><name sortKey="Taylor, Jane R" sort="Taylor, Jane R" uniqKey="Taylor J" first="Jane R." last="Taylor">Jane R. Taylor</name><affiliation><mods:affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</mods:affiliation></affiliation></author><author><name sortKey="Elsworth, John D" sort="Elsworth, John D" uniqKey="Elsworth J" first="John D." last="Elsworth">John D. Elsworth</name><affiliation><mods:affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</mods:affiliation></affiliation></author><author><name sortKey="Sladek Jr, John R" sort="Sladek Jr, John R" uniqKey="Sladek Jr J" first="John R." last="Sladek Jr.">John R. Sladek Jr.</name><affiliation><mods:affiliation>Department of Neuroscience, University of Health Sciences/The Chicago Medical School, North Chicago, IL, 60064, USA</mods:affiliation></affiliation></author><author><name sortKey="Collier, Timothy J" sort="Collier, Timothy J" uniqKey="Collier T" first="Timothy J." last="Collier">Timothy J. Collier</name><affiliation><mods:affiliation>Department of Neurological Sciences, Rush-Presbyterian-St. Lukes Medical Center, Rush University, Chicago, IL 60612 USA</mods:affiliation></affiliation></author><author><name sortKey="Roth, Robert H" sort="Roth, Robert H" uniqKey="Roth R" first="Robert H." last="Roth">Robert H. Roth</name><affiliation><mods:affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</mods:affiliation></affiliation></author><author><name sortKey="Redmond Jr, D Eugene" sort="Redmond Jr, D Eugene" uniqKey="Redmond Jr D" first="D. Eugene" last="Redmond Jr.">D. 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Taylor</name><affiliation><mods:affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</mods:affiliation></affiliation></author><author><name sortKey="Elsworth, John D" sort="Elsworth, John D" uniqKey="Elsworth J" first="John D." last="Elsworth">John D. Elsworth</name><affiliation><mods:affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</mods:affiliation></affiliation></author><author><name sortKey="Sladek Jr, John R" sort="Sladek Jr, John R" uniqKey="Sladek Jr J" first="John R." last="Sladek Jr.">John R. Sladek Jr.</name><affiliation><mods:affiliation>Department of Neuroscience, University of Health Sciences/The Chicago Medical School, North Chicago, IL, 60064, USA</mods:affiliation></affiliation></author><author><name sortKey="Collier, Timothy J" sort="Collier, Timothy J" uniqKey="Collier T" first="Timothy J." last="Collier">Timothy J. Collier</name><affiliation><mods:affiliation>Department of Neurological Sciences, Rush-Presbyterian-St. Lukes Medical Center, Rush University, Chicago, IL 60612 USA</mods:affiliation></affiliation></author><author><name sortKey="Roth, Robert H" sort="Roth, Robert H" uniqKey="Roth R" first="Robert H." last="Roth">Robert H. Roth</name><affiliation><mods:affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</mods:affiliation></affiliation></author><author><name sortKey="Redmond Jr, D Eugene" sort="Redmond Jr, D Eugene" uniqKey="Redmond Jr D" first="D. Eugene" last="Redmond Jr.">D. Eugene Redmond Jr.</name><affiliation><mods:affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Cell Transplantation</title><title level="j" type="abbrev">CTR</title><idno type="ISSN">0963-6897</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1994">1994</date><biblScope unit="volume">4</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="13">13</biblScope><biblScope unit="page" to="26">26</biblScope></imprint><idno type="ISSN">0963-6897</idno></series><idno type="istex">B38C41BCF6CC1DFCAD8A34DAFEFC922707C7B062</idno><idno type="DOI">10.1016/0963-6897(94)00035-I</idno><idno type="PII">0963-6897(94)00035-I</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0963-6897</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinsonism has been reported to improve following transplantation of fetal mesencephalic tissue into the striatum of MPTP-exposed monkeys and humans and in patients with idiopathic Parkinson's disease. While there is good evidence for the survival of grafted tyrosine hydroxy-lase (TH)-positive cells in animal studies, it is not known whether they produce neuronal effects that account for behavioral improvement after transplantation or whether spontaneous or graft-induced changes in the host striatum are at least partly responsible. Are neuronal synaptic connections and dopamine release necessary, or would “toenails and talcum powder” do the job equally well? We have addressed these questions by studying several types of implantation surgeries, including sham surgery, the implantation of cerebellar tissue, and the implantation of mesencephalic TH-positive fetal tissue of various gestational ages into the striatum. Adult male African green monkeys received systemic MPTP administration (cumulative doses of 2.0–2.5 mg/kg) prior to these stereotaxic surgical manipulations. Subjects were matched for quantitative behavioral deficits prior to surgery. Subjects were examined and assessments made by “blinded” observers who scored individual spontaneous and elicited behaviors. Observers were trained and tested repeatedly for inter-rater reliability. A “parkinsonian summary score” derived and determined using a principal component factor analysis of a large sample of data from MPTP-treated and normal monkeys of the same species was used to assess behavior. Postmortem brain tissue was prepared for biochemical analysis of dopamine concentrations and TH immunohistochemical studies. The most dramatic improvement was seen in monkeys with “early” (<4 cm fetal crown rump length) surviving substantia nigra grafts in the caudate nucleus. Some behavioral improvements were seen in MPTP-treated sham-operated monkeys, cerebellar-grafted monkeys, and “later” (>14 cm fetal crown rump length) substantia nigra-grafted monkeys. These changes in monkeys which did not have surviving dopamine-producing grafts probably represent the recovery capacity of MPTP-treated host brain during this time interval since un-operated subjects showed similar changes. More variable effects were seen with substantia nigra grafts in the putamen. The most consistent correlate of behavioral improvement in all experimental groups was elevation in dopamine concentrations near the grafts compared with a distant striatal location which is believed to represent the depletion without the effects of the grafts. While these data do not establish the precise mechanism of action, they point to a hierarchy of factors which provide increasingly larger restorative effects, including sprouting of host neurons and increased dopamine production by grafted fetal dopamine neurons. Sham surgery appears to be significantly less effective than early fetal mesencephalic tissue which survives and releases dopamine.</div></front></TEI><istex><corpusName>elsevier</corpusName><author><json:item><name>Jane R. Taylor</name><affiliations><json:string>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</json:string></affiliations></json:item><json:item><name>John D. Elsworth</name><affiliations><json:string>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</json:string></affiliations></json:item><json:item><name>John R. Sladek, Jr.</name><affiliations><json:string>Department of Neuroscience, University of Health Sciences/The Chicago Medical School, North Chicago, IL, 60064, USA</json:string></affiliations></json:item><json:item><name>Timothy J. Collier</name><affiliations><json:string>Department of Neurological Sciences, Rush-Presbyterian-St. Lukes Medical Center, Rush University, Chicago, IL 60612 USA</json:string></affiliations></json:item><json:item><name>Robert H. Roth</name><affiliations><json:string>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</json:string></affiliations></json:item><json:item><name>D.Eugene Redmond, Jr.</name><affiliations><json:string>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>Fetal neural tissue</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Behavior</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Sham surgery</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Neural grafts</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Caudate nucleus</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Putamen</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Parkinson's disease</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>MPTP</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Monkey</value></json:item></subject><language><json:string>eng</json:string></language><abstract>Parkinsonism has been reported to improve following transplantation of fetal mesencephalic tissue into the striatum of MPTP-exposed monkeys and humans and in patients with idiopathic Parkinson's disease. While there is good evidence for the survival of grafted tyrosine hydroxy-lase (TH)-positive cells in animal studies, it is not known whether they produce neuronal effects that account for behavioral improvement after transplantation or whether spontaneous or graft-induced changes in the host striatum are at least partly responsible. Are neuronal synaptic connections and dopamine release necessary, or would “toenails and talcum powder” do the job equally well? We have addressed these questions by studying several types of implantation surgeries, including sham surgery, the implantation of cerebellar tissue, and the implantation of mesencephalic TH-positive fetal tissue of various gestational ages into the striatum. Adult male African green monkeys received systemic MPTP administration (cumulative doses of 2.0–2.5 mg/kg) prior to these stereotaxic surgical manipulations. Subjects were matched for quantitative behavioral deficits prior to surgery. Subjects were examined and assessments made by “blinded” observers who scored individual spontaneous and elicited behaviors. Observers were trained and tested repeatedly for inter-rater reliability. A “parkinsonian summary score” derived and determined using a principal component factor analysis of a large sample of data from MPTP-treated and normal monkeys of the same species was used to assess behavior. Postmortem brain tissue was prepared for biochemical analysis of dopamine concentrations and TH immunohistochemical studies. The most dramatic improvement was seen in monkeys with “early” (>4 cm fetal crown rump length) surviving substantia nigra grafts in the caudate nucleus. Some behavioral improvements were seen in MPTP-treated sham-operated monkeys, cerebellar-grafted monkeys, and “later” (>14 cm fetal crown rump length) substantia nigra-grafted monkeys. These changes in monkeys which did not have surviving dopamine-producing grafts probably represent the recovery capacity of MPTP-treated host brain during this time interval since un-operated subjects showed similar changes. More variable effects were seen with substantia nigra grafts in the putamen. The most consistent correlate of behavioral improvement in all experimental groups was elevation in dopamine concentrations near the grafts compared with a distant striatal location which is believed to represent the depletion without the effects of the grafts. While these data do not establish the precise mechanism of action, they point to a hierarchy of factors which provide increasingly larger restorative effects, including sprouting of host neurons and increased dopamine production by grafted fetal dopamine neurons. Sham surgery appears to be significantly less effective than early fetal mesencephalic tissue which survives and releases dopamine.</abstract><qualityIndicators><score>8</score><pdfVersion>1.2</pdfVersion><pdfPageSize>612 x 828 pts</pdfPageSize><refBibsNative>true</refBibsNative><keywordCount>9</keywordCount><abstractCharCount>2995</abstractCharCount><pdfWordCount>7578</pdfWordCount><pdfCharCount>50695</pdfCharCount><pdfPageCount>14</pdfPageCount><abstractWordCount>414</abstractWordCount></qualityIndicators><title>Sham surgery does not ameliorate MPTP-induced behavioral deficits in 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level="a">Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>ELSEVIER</publisher><availability><p>ELSEVIER</p></availability><date>1995</date></publicationStmt><notesStmt><note>Presented at the first meeting of the American Society for Neural Transplantation.</note><note type="content">Section title: Original contribution</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a">Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys</title><author><persName><forename type="first">Jane R.</forename><surname>Taylor</surname></persName><note type="correspondence"><p>Correspondence should be addressed to Jane Rebecca Taylor, Ph.D., Neurobehavior Laboratory, Department of Psychiatry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.</p></note><affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</affiliation></author><author><persName><forename type="first">John D.</forename><surname>Elsworth</surname></persName><affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</affiliation></author><author><persName><forename type="first">John R.</forename><surname>Sladek, Jr.</surname></persName><affiliation>Department of Neuroscience, University of Health Sciences/The Chicago Medical School, North Chicago, IL, 60064, USA</affiliation></author><author><persName><forename type="first">Timothy J.</forename><surname>Collier</surname></persName><affiliation>Department of Neurological Sciences, Rush-Presbyterian-St. Lukes Medical Center, Rush University, Chicago, IL 60612 USA</affiliation></author><author><persName><forename type="first">Robert H.</forename><surname>Roth</surname></persName><affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</affiliation></author><author><persName><forename type="first">D.Eugene</forename><surname>Redmond, Jr.</surname></persName><affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</affiliation></author></analytic><monogr><title level="j">Cell Transplantation</title><title level="j" type="abbrev">CTR</title><idno type="pISSN">0963-6897</idno><idno type="PII">S0963-6897(00)X0012-7</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1994"></date><biblScope unit="volume">4</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="13">13</biblScope><biblScope unit="page" to="26">26</biblScope></imprint></monogr><idno type="istex">B38C41BCF6CC1DFCAD8A34DAFEFC922707C7B062</idno><idno type="DOI">10.1016/0963-6897(94)00035-I</idno><idno type="PII">0963-6897(94)00035-I</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1995</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Parkinsonism has been reported to improve following transplantation of fetal mesencephalic tissue into the striatum of MPTP-exposed monkeys and humans and in patients with idiopathic Parkinson's disease. While there is good evidence for the survival of grafted tyrosine hydroxy-lase (TH)-positive cells in animal studies, it is not known whether they produce neuronal effects that account for behavioral improvement after transplantation or whether spontaneous or graft-induced changes in the host striatum are at least partly responsible. Are neuronal synaptic connections and dopamine release necessary, or would “toenails and talcum powder” do the job equally well? We have addressed these questions by studying several types of implantation surgeries, including sham surgery, the implantation of cerebellar tissue, and the implantation of mesencephalic TH-positive fetal tissue of various gestational ages into the striatum. Adult male African green monkeys received systemic MPTP administration (cumulative doses of 2.0–2.5 mg/kg) prior to these stereotaxic surgical manipulations. Subjects were matched for quantitative behavioral deficits prior to surgery. Subjects were examined and assessments made by “blinded” observers who scored individual spontaneous and elicited behaviors. Observers were trained and tested repeatedly for inter-rater reliability. A “parkinsonian summary score” derived and determined using a principal component factor analysis of a large sample of data from MPTP-treated and normal monkeys of the same species was used to assess behavior. Postmortem brain tissue was prepared for biochemical analysis of dopamine concentrations and TH immunohistochemical studies. The most dramatic improvement was seen in monkeys with “early” (<4 cm fetal crown rump length) surviving substantia nigra grafts in the caudate nucleus. Some behavioral improvements were seen in MPTP-treated sham-operated monkeys, cerebellar-grafted monkeys, and “later” (>14 cm fetal crown rump length) substantia nigra-grafted monkeys. These changes in monkeys which did not have surviving dopamine-producing grafts probably represent the recovery capacity of MPTP-treated host brain during this time interval since un-operated subjects showed similar changes. More variable effects were seen with substantia nigra grafts in the putamen. The most consistent correlate of behavioral improvement in all experimental groups was elevation in dopamine concentrations near the grafts compared with a distant striatal location which is believed to represent the depletion without the effects of the grafts. While these data do not establish the precise mechanism of action, they point to a hierarchy of factors which provide increasingly larger restorative effects, including sprouting of host neurons and increased dopamine production by grafted fetal dopamine neurons. Sham surgery appears to be significantly less effective than early fetal mesencephalic tissue which survives and releases dopamine.</p></abstract><textClass><keywords scheme="keyword"><list><head>Keywords</head><item><term>Fetal neural tissue</term></item><item><term>Behavior</term></item><item><term>Sham surgery</term></item><item><term>Neural grafts</term></item><item><term>Caudate nucleus</term></item><item><term>Putamen</term></item><item><term>Parkinson's disease</term></item><item><term>MPTP</term></item><item><term>Monkey</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="1994-09-06">Registration</change><change when="1994">Published</change></revisionDesc></teiHeader></istex:fulltextTEI></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier, elements deleted: tail"><istex:xmlDeclaration>version="1.0" encoding="utf-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 4.5.2//EN//XML" URI="art452.dtd" name="istex:docType"></istex:docType><istex:document><converted-article version="4.5.2" docsubtype="fla"><item-info><jid>CTR</jid><aid>9400035I</aid><ce:pii>0963-6897(94)00035-I</ce:pii><ce:doi>10.1016/0963-6897(94)00035-I</ce:doi><ce:copyright type="unknown" year="1995"></ce:copyright></item-info><head><ce:article-footnote><ce:label>☆</ce:label><ce:note-para>Presented at the first meeting of the American Society for Neural Transplantation.</ce:note-para></ce:article-footnote><ce:dochead><ce:textfn>Original contribution</ce:textfn></ce:dochead><ce:title>Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys</ce:title><ce:author-group><ce:author><ce:given-name>Jane R.</ce:given-name><ce:surname>Taylor</ce:surname><ce:cross-ref refid="COR1"><ce:sup>1</ce:sup></ce:cross-ref><ce:cross-ref refid="AFF1"><ce:sup>∗</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>John D.</ce:given-name><ce:surname>Elsworth</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>∗</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>John R.</ce:given-name><ce:surname>Sladek</ce:surname><ce:suffix>Jr.</ce:suffix><ce:cross-ref refid="AFF2"><ce:sup>†</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Timothy J.</ce:given-name><ce:surname>Collier</ce:surname><ce:cross-ref refid="AFF3"><ce:sup>‡</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Robert H.</ce:given-name><ce:surname>Roth</ce:surname><ce:cross-ref refid="AFF1"><ce:sup>∗</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>D.Eugene</ce:given-name><ce:surname>Redmond</ce:surname><ce:suffix>Jr.</ce:suffix><ce:cross-ref refid="AFF1"><ce:sup>∗</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="AFF1"><ce:label>a</ce:label><ce:textfn>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF2"><ce:label>b</ce:label><ce:textfn>Department of Neuroscience, University of Health Sciences/The Chicago Medical School, North Chicago, IL, 60064, USA</ce:textfn></ce:affiliation><ce:affiliation id="AFF3"><ce:label>c</ce:label><ce:textfn>Department of Neurological Sciences, Rush-Presbyterian-St. Lukes Medical Center, Rush University, Chicago, IL 60612 USA</ce:textfn></ce:affiliation><ce:correspondence id="COR1"><ce:label>1</ce:label><ce:text>Correspondence should be addressed to Jane Rebecca Taylor, Ph.D., Neurobehavior Laboratory, Department of Psychiatry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.</ce:text></ce:correspondence></ce:author-group><ce:date-accepted day="6" month="9" year="1994"></ce:date-accepted><ce:abstract><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para>Parkinsonism has been reported to improve following transplantation of fetal mesencephalic tissue into the striatum of MPTP-exposed monkeys and humans and in patients with idiopathic Parkinson's disease. While there is good evidence for the survival of grafted tyrosine hydroxy-lase (TH)-positive cells in animal studies, it is not known whether they produce neuronal effects that account for behavioral improvement after transplantation or whether spontaneous or graft-induced changes in the host striatum are at least partly responsible. Are neuronal synaptic connections and dopamine release necessary, or would “toenails and talcum powder” do the job equally well? We have addressed these questions by studying several types of implantation surgeries, including sham surgery, the implantation of cerebellar tissue, and the implantation of mesencephalic TH-positive fetal tissue of various gestational ages into the striatum. Adult male African green monkeys received systemic MPTP administration (cumulative doses of 2.0–2.5 mg/kg) prior to these stereotaxic surgical manipulations. Subjects were matched for quantitative behavioral deficits prior to surgery. Subjects were examined and assessments made by “blinded” observers who scored individual spontaneous and elicited behaviors. Observers were trained and tested repeatedly for inter-rater reliability. A “parkinsonian summary score” derived and determined using a principal component factor analysis of a large sample of data from MPTP-treated and normal monkeys of the same species was used to assess behavior. Postmortem brain tissue was prepared for biochemical analysis of dopamine concentrations and TH immunohistochemical studies. The most dramatic improvement was seen in monkeys with “early” (<4 cm fetal crown rump length) surviving substantia nigra grafts in the caudate nucleus. Some behavioral improvements were seen in MPTP-treated sham-operated monkeys, cerebellar-grafted monkeys, and “later” (>14 cm fetal crown rump length) substantia nigra-grafted monkeys. These changes in monkeys which did not have surviving dopamine-producing grafts probably represent the recovery capacity of MPTP-treated host brain during this time interval since un-operated subjects showed similar changes. More variable effects were seen with substantia nigra grafts in the putamen. The most consistent correlate of behavioral improvement in all experimental groups was elevation in dopamine concentrations near the grafts compared with a distant striatal location which is believed to represent the depletion without the effects of the grafts. While these data do not establish the precise mechanism of action, they point to a hierarchy of factors which provide increasingly larger restorative effects, including sprouting of host neurons and increased dopamine production by grafted fetal dopamine neurons. Sham surgery appears to be significantly less effective than early fetal mesencephalic tissue which survives and releases dopamine.</ce:simple-para></ce:abstract-sec></ce:abstract><ce:keywords><ce:section-title>Keywords</ce:section-title><ce:keyword><ce:text>Fetal neural tissue</ce:text></ce:keyword><ce:keyword><ce:text>Behavior</ce:text></ce:keyword><ce:keyword><ce:text>Sham surgery</ce:text></ce:keyword><ce:keyword><ce:text>Neural grafts</ce:text></ce:keyword><ce:keyword><ce:text>Caudate nucleus</ce:text></ce:keyword><ce:keyword><ce:text>Putamen</ce:text></ce:keyword><ce:keyword><ce:text>Parkinson's disease</ce:text></ce:keyword><ce:keyword><ce:text>MPTP</ce:text></ce:keyword><ce:keyword><ce:text>Monkey</ce:text></ce:keyword></ce:keywords></head></converted-article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Sham surgery does not ameliorate MPTP-induced behavioral deficits in monkeys</title></titleInfo><name type="personal"><namePart type="given">Jane R.</namePart><namePart type="family">Taylor</namePart><affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</affiliation><description>Correspondence should be addressed to Jane Rebecca Taylor, Ph.D., Neurobehavior Laboratory, Department of Psychiatry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.</description><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John D.</namePart><namePart type="family">Elsworth</namePart><affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">John R.</namePart><namePart type="family">Sladek, Jr.</namePart><affiliation>Department of Neuroscience, University of Health Sciences/The Chicago Medical School, North Chicago, IL, 60064, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Timothy J.</namePart><namePart type="family">Collier</namePart><affiliation>Department of Neurological Sciences, Rush-Presbyterian-St. Lukes Medical Center, Rush University, Chicago, IL 60612 USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Robert H.</namePart><namePart type="family">Roth</namePart><affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">D.Eugene</namePart><namePart type="family">Redmond, Jr.</namePart><affiliation>Department of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article"></genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1994</dateIssued><dateValid encoding="w3cdtf">1994-09-06</dateValid><copyrightDate encoding="w3cdtf">1995</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType></physicalDescription><abstract lang="en">Parkinsonism has been reported to improve following transplantation of fetal mesencephalic tissue into the striatum of MPTP-exposed monkeys and humans and in patients with idiopathic Parkinson's disease. While there is good evidence for the survival of grafted tyrosine hydroxy-lase (TH)-positive cells in animal studies, it is not known whether they produce neuronal effects that account for behavioral improvement after transplantation or whether spontaneous or graft-induced changes in the host striatum are at least partly responsible. Are neuronal synaptic connections and dopamine release necessary, or would “toenails and talcum powder” do the job equally well? We have addressed these questions by studying several types of implantation surgeries, including sham surgery, the implantation of cerebellar tissue, and the implantation of mesencephalic TH-positive fetal tissue of various gestational ages into the striatum. Adult male African green monkeys received systemic MPTP administration (cumulative doses of 2.0–2.5 mg/kg) prior to these stereotaxic surgical manipulations. Subjects were matched for quantitative behavioral deficits prior to surgery. Subjects were examined and assessments made by “blinded” observers who scored individual spontaneous and elicited behaviors. Observers were trained and tested repeatedly for inter-rater reliability. A “parkinsonian summary score” derived and determined using a principal component factor analysis of a large sample of data from MPTP-treated and normal monkeys of the same species was used to assess behavior. Postmortem brain tissue was prepared for biochemical analysis of dopamine concentrations and TH immunohistochemical studies. The most dramatic improvement was seen in monkeys with “early” (<4 cm fetal crown rump length) surviving substantia nigra grafts in the caudate nucleus. Some behavioral improvements were seen in MPTP-treated sham-operated monkeys, cerebellar-grafted monkeys, and “later” (>14 cm fetal crown rump length) substantia nigra-grafted monkeys. These changes in monkeys which did not have surviving dopamine-producing grafts probably represent the recovery capacity of MPTP-treated host brain during this time interval since un-operated subjects showed similar changes. More variable effects were seen with substantia nigra grafts in the putamen. The most consistent correlate of behavioral improvement in all experimental groups was elevation in dopamine concentrations near the grafts compared with a distant striatal location which is believed to represent the depletion without the effects of the grafts. While these data do not establish the precise mechanism of action, they point to a hierarchy of factors which provide increasingly larger restorative effects, including sprouting of host neurons and increased dopamine production by grafted fetal dopamine neurons. Sham surgery appears to be significantly less effective than early fetal mesencephalic tissue which survives and releases dopamine.</abstract><note>Presented at the first meeting of the American Society for Neural Transplantation.</note><note type="content">Section title: Original contribution</note><subject><genre>Keywords</genre><topic>Fetal neural tissue</topic><topic>Behavior</topic><topic>Sham surgery</topic><topic>Neural grafts</topic><topic>Caudate nucleus</topic><topic>Putamen</topic><topic>Parkinson's disease</topic><topic>MPTP</topic><topic>Monkey</topic></subject><relatedItem type="host"><titleInfo><title>Cell Transplantation</title></titleInfo><titleInfo type="abbreviated"><title>CTR</title></titleInfo><genre type="Journal">journal</genre><originInfo><dateIssued encoding="w3cdtf">199501</dateIssued></originInfo><identifier type="ISSN">0963-6897</identifier><identifier type="PII">S0963-6897(00)X0012-7</identifier><part><date>199501</date><detail type="issue"><title>Neural Transplantation into the CNS</title></detail><detail type="volume"><number>4</number><caption>vol.</caption></detail><detail type="issue"><number>1</number><caption>no.</caption></detail><extent unit="issue pages"><start>1</start><end>154</end></extent><extent unit="pages"><start>13</start><end>26</end></extent></part></relatedItem><identifier type="istex">B38C41BCF6CC1DFCAD8A34DAFEFC922707C7B062</identifier><identifier type="DOI">10.1016/0963-6897(94)00035-I</identifier><identifier type="PII">0963-6897(94)00035-I</identifier><recordInfo><recordContentSource>ELSEVIER</recordContentSource></recordInfo></mods></metadata><enrichments><istex:catWosTEI uri="https://api.istex.fr/document/B38C41BCF6CC1DFCAD8A34DAFEFC922707C7B062/enrichments/catWos"><teiHeader><profileDesc><textClass><classCode scheme="WOS">MEDICINE, RESEARCH & EXPERIMENTAL</classCode><classCode scheme="WOS">TRANSPLANTATION</classCode><classCode scheme="WOS">CELL & TISSUE ENGINEERING</classCode><classCode scheme="WOS">CELL BIOLOGY</classCode></textClass></profileDesc></teiHeader></istex:catWosTEI></enrichments><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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