Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy.
Identifieur interne : 001E27 ( Ncbi/Checkpoint ); précédent : 001E26; suivant : 001E28Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy.
Auteurs : Nadia Stefanova [Autriche] ; Markus Reindl ; Manuela Neumann ; Philipp J. Kahle ; Werner Poewe [Autriche] ; Gregor K. WenningSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 2007.
English descriptors
- KwdEn :
- Aged, Animals, Corpus Striatum (metabolism), Corpus Striatum (pathology), Disease Progression, Dopamine (physiology), Female, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microglia (pathology), Middle Aged, Minocycline (pharmacology), Multiple System Atrophy (drug therapy), Multiple System Atrophy (metabolism), Multiple System Atrophy (pathology), Nerve Degeneration (drug therapy), Nerve Degeneration (metabolism), Nerve Degeneration (pathology), Neuroprotective Agents (pharmacology), Nitric Oxide Synthase Type II (metabolism), Oligodendroglia (metabolism), Oligodendroglia (pathology), Toll-Like Receptor 4 (metabolism), alpha-Synuclein (genetics), alpha-Synuclein (metabolism).
- MESH :
- chemical , genetics : alpha-Synuclein.
- chemical , metabolism : Nitric Oxide Synthase Type II, Toll-Like Receptor 4, alpha-Synuclein.
- chemical , pharmacology : Minocycline, Neuroprotective Agents.
- chemical , physiology : Dopamine.
- drug therapy : Multiple System Atrophy, Nerve Degeneration.
- metabolism : Corpus Striatum, Multiple System Atrophy, Nerve Degeneration, Oligodendroglia.
- pathology : Corpus Striatum, Microglia, Multiple System Atrophy, Nerve Degeneration, Oligodendroglia.
- Aged, Animals, Disease Progression, Female, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Middle Aged.
Abstract
The role of microglial activation in multiple system atrophy (MSA) was investigated in a transgenic mouse model featuring oligodendroglial alpha-synuclein inclusions and loss of midbrain dopaminergic neurons by means of histopathology and morphometric analysis. Our findings demonstrate early progressive microglial activation in substantia nigra pars compacta (SNc) associated with increased expression of iNOS and correlating with dopaminergic neuronal loss. Suppression of microglial activation by early long-term minocycline treatment protected dopaminergic SNc neurons. The results suggest that oligodendroglial overexpression of alpha-synuclein may induce neuroinflammation related to nitrosive stress which is likely to contribute to neurodegeneration in MSA. Further, we detected increased toll-like receptor 4 immunoreactivity in both transgenic mice and MSA brains indicating a possible signaling pathway in MSA which needs to be further studied as a candidate target for neuroprotective interventions.
DOI: 10.1002/mds.21671
PubMed: 17853477
Affiliations:
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Kahle</name></author><author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name><affiliation><country>Autriche</country><placeName><settlement type="city">Innsbruck</settlement><region nuts="2" type="region">Tyrol (Land)</region></placeName><orgName type="university">Université de médecine d'Innsbruck</orgName></affiliation></author><author><name sortKey="Wenning, Gregor K" sort="Wenning, Gregor K" uniqKey="Wenning G" first="Gregor K" last="Wenning">Gregor K. 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Kahle</name></author><author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name><affiliation><country>Autriche</country><placeName><settlement type="city">Innsbruck</settlement><region nuts="2" type="region">Tyrol (Land)</region></placeName><orgName type="university">Université de médecine d'Innsbruck</orgName></affiliation></author><author><name sortKey="Wenning, Gregor K" sort="Wenning, Gregor K" uniqKey="Wenning G" first="Gregor K" last="Wenning">Gregor K. Wenning</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="2007" type="published">2007</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Animals</term><term>Corpus Striatum (metabolism)</term><term>Corpus Striatum (pathology)</term><term>Disease Progression</term><term>Dopamine (physiology)</term><term>Female</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term><term>Microglia (pathology)</term><term>Middle Aged</term><term>Minocycline (pharmacology)</term><term>Multiple System Atrophy (drug therapy)</term><term>Multiple System Atrophy (metabolism)</term><term>Multiple System Atrophy (pathology)</term><term>Nerve Degeneration (drug therapy)</term><term>Nerve Degeneration (metabolism)</term><term>Nerve Degeneration (pathology)</term><term>Neuroprotective Agents (pharmacology)</term><term>Nitric Oxide Synthase Type II (metabolism)</term><term>Oligodendroglia (metabolism)</term><term>Oligodendroglia (pathology)</term><term>Toll-Like Receptor 4 (metabolism)</term><term>alpha-Synuclein (genetics)</term><term>alpha-Synuclein (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Nitric Oxide Synthase Type II</term><term>Toll-Like Receptor 4</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Minocycline</term><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Multiple System Atrophy</term><term>Nerve Degeneration</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term><term>Multiple System Atrophy</term><term>Nerve Degeneration</term><term>Oligodendroglia</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Corpus Striatum</term><term>Microglia</term><term>Multiple System Atrophy</term><term>Nerve Degeneration</term><term>Oligodendroglia</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Animals</term><term>Disease Progression</term><term>Female</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Transgenic</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The role of microglial activation in multiple system atrophy (MSA) was investigated in a transgenic mouse model featuring oligodendroglial alpha-synuclein inclusions and loss of midbrain dopaminergic neurons by means of histopathology and morphometric analysis. Our findings demonstrate early progressive microglial activation in substantia nigra pars compacta (SNc) associated with increased expression of iNOS and correlating with dopaminergic neuronal loss. Suppression of microglial activation by early long-term minocycline treatment protected dopaminergic SNc neurons. The results suggest that oligodendroglial overexpression of alpha-synuclein may induce neuroinflammation related to nitrosive stress which is likely to contribute to neurodegeneration in MSA. Further, we detected increased toll-like receptor 4 immunoreactivity in both transgenic mice and MSA brains indicating a possible signaling pathway in MSA which needs to be further studied as a candidate target for neuroprotective interventions.</div></front></TEI><affiliations><list><country><li>Autriche</li></country><region><li>Tyrol (Land)</li></region><settlement><li>Innsbruck</li></settlement><orgName><li>Université de médecine d'Innsbruck</li></orgName></list><tree><noCountry><name sortKey="Kahle, Philipp J" sort="Kahle, Philipp J" uniqKey="Kahle P" first="Philipp J" last="Kahle">Philipp J. Kahle</name><name sortKey="Neumann, Manuela" sort="Neumann, Manuela" uniqKey="Neumann M" first="Manuela" last="Neumann">Manuela Neumann</name><name sortKey="Reindl, Markus" sort="Reindl, Markus" uniqKey="Reindl M" first="Markus" last="Reindl">Markus Reindl</name><name sortKey="Wenning, Gregor K" sort="Wenning, Gregor K" uniqKey="Wenning G" first="Gregor K" last="Wenning">Gregor K. Wenning</name></noCountry><country name="Autriche"><noRegion><name sortKey="Stefanova, Nadia" sort="Stefanova, Nadia" uniqKey="Stefanova N" first="Nadia" last="Stefanova">Nadia Stefanova</name></noRegion><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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