Systemic administration of a proteasome inhibitor does not cause nigrostriatal dopamine degeneration
Identifieur interne : 002639 ( Main/Exploration ); précédent : 002638; suivant : 002640Systemic administration of a proteasome inhibitor does not cause nigrostriatal dopamine degeneration
Auteurs : Brian N. Mathur [États-Unis] ; M. Diana Neely [États-Unis] ; Melanie Dyllick-Brenzinger [Canada] ; Anurag Tandon [Canada] ; Ariel Y. Deutch [États-Unis]Source :
- Brain research [ 0006-8993 ] ; 2007.
Descripteurs français
- Pascal (Inist)
- Animal, Corps strié, Dopamine, Dégénérescence, Inhibiteur enzyme, Locus niger, Multicatalytic endopeptidase complex, Parkinson maladie, Rat, Tyrosine 3-monooxygenase, Voie nigrostriatale, Dopamine, Dégénérescence, Corps strié, Locus niger, Tyrosine 3-monooxygenase, Parkinson maladie, Rat, Inhibiteur enzyme, Animal.
English descriptors
- KwdEn :
Abstract
Proteasomal dysfunction has been suggested to contribute to the degeneration of nigrostriatal dopamine neurons in Parkinson's disease. A recent study reported that systemic treatment of rats with the proteasome inhibitor Z-lle-Glu(OtBu)-Ala-Leu-al (PSI) causes a slowly progressive degeneration of nigrostriatal dopamine neurons, the presence of inclusion bodies in dopamine neurons, and motor impairment. We examined in vitro and in uiuo the effects of PSI on nigrostriatal dopamine neurons. Mass spectrometric analysis was employed to verify the authenticity of the PSI compound. PSI was non-specifically toxic to neurons in ventral mesencephalic organotypic slice cultures, indicating that impairment of proteasome function in vitro is toxic. Moreover, systemic administration of PSI transiently decreased brain proteasome activity. Systemic treatment of rats with PSI did not, however, result in any biochemical or anatomical evidence of lesions of nigrostriatal dopamine neurons, nor were any changes in locomotor activity observed. These data suggest that systemic administration of proteasome inhibitors to normal adult rats does not reliably cause an animal model ofparkinsonism.
Affiliations:
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Mathur</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Program in Neuroscience and Departments of Psychiatry and Pharmacology, Vanderbilt University Medical Center</s1><s2>Nashville, TN</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Nashville, TN</wicri:noRegion></affiliation></author><author><name sortKey="Neely, M Diana" sort="Neely, M Diana" uniqKey="Neely M" first="M. Diana" last="Neely">M. Diana Neely</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Program in Neuroscience and Departments of Psychiatry and Pharmacology, Vanderbilt University Medical Center</s1><s2>Nashville, TN</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Nashville, TN</wicri:noRegion></affiliation></author><author><name sortKey="Dyllick Brenzinger, Melanie" sort="Dyllick Brenzinger, Melanie" uniqKey="Dyllick Brenzinger M" first="Melanie" last="Dyllick-Brenzinger">Melanie Dyllick-Brenzinger</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Research in Neurodegenerative Diseases, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Center for Research in Neurodegenerative Diseases, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Deutch, Ariel Y" sort="Deutch, Ariel Y" uniqKey="Deutch A" first="Ariel Y." last="Deutch">Ariel Y. Deutch</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Program in Neuroscience and Departments of Psychiatry and Pharmacology, Vanderbilt University Medical Center</s1><s2>Nashville, TN</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Nashville, TN</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Brain research</title><title level="j" type="abbreviated">Brain res.</title><idno type="ISSN">0006-8993</idno><imprint><date when="2007">2007</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Brain research</title><title level="j" type="abbreviated">Brain res.</title><idno type="ISSN">0006-8993</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animal</term><term>Corpus striatum</term><term>Degeneration</term><term>Dopamine</term><term>Enzyme inhibitor</term><term>Locus niger</term><term>Multicatalytic endopeptidase complex</term><term>Nigrostriatal pathway</term><term>Parkinson disease</term><term>Rat</term><term>Tyrosine 3-monooxygenase</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Animal</term><term>Corps strié</term><term>Dopamine</term><term>Dégénérescence</term><term>Inhibiteur enzyme</term><term>Locus niger</term><term>Multicatalytic endopeptidase complex</term><term>Parkinson maladie</term><term>Rat</term><term>Tyrosine 3-monooxygenase</term><term>Voie nigrostriatale</term><term>Dopamine</term><term>Dégénérescence</term><term>Corps strié</term><term>Locus niger</term><term>Tyrosine 3-monooxygenase</term><term>Parkinson maladie</term><term>Rat</term><term>Inhibiteur enzyme</term><term>Animal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Proteasomal dysfunction has been suggested to contribute to the degeneration of nigrostriatal dopamine neurons in Parkinson's disease. A recent study reported that systemic treatment of rats with the proteasome inhibitor Z-lle-Glu(OtBu)-Ala-Leu-al (PSI) causes a slowly progressive degeneration of nigrostriatal dopamine neurons, the presence of inclusion bodies in dopamine neurons, and motor impairment. We examined in vitro and in uiuo the effects of PSI on nigrostriatal dopamine neurons. Mass spectrometric analysis was employed to verify the authenticity of the PSI compound. PSI was non-specifically toxic to neurons in ventral mesencephalic organotypic slice cultures, indicating that impairment of proteasome function in vitro is toxic. Moreover, systemic administration of PSI transiently decreased brain proteasome activity. Systemic treatment of rats with PSI did not, however, result in any biochemical or anatomical evidence of lesions of nigrostriatal dopamine neurons, nor were any changes in locomotor activity observed. These data suggest that systemic administration of proteasome inhibitors to normal adult rats does not reliably cause an animal model ofparkinsonism.</div></front></TEI><affiliations><list><country><li>Canada</li><li>États-Unis</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="États-Unis"><noRegion><name sortKey="Mathur, Brian N" sort="Mathur, Brian N" uniqKey="Mathur B" first="Brian N." last="Mathur">Brian N. Mathur</name></noRegion><name sortKey="Deutch, Ariel Y" sort="Deutch, Ariel Y" uniqKey="Deutch A" first="Ariel Y." last="Deutch">Ariel Y. Deutch</name><name sortKey="Neely, M Diana" sort="Neely, M Diana" uniqKey="Neely M" first="M. Diana" last="Neely">M. Diana Neely</name></country><country name="Canada"><region name="Ontario"><name sortKey="Dyllick Brenzinger, Melanie" sort="Dyllick Brenzinger, Melanie" uniqKey="Dyllick Brenzinger M" first="Melanie" last="Dyllick-Brenzinger">Melanie Dyllick-Brenzinger</name></region><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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