MFGE8 does not orchestrate clearance of apoptotic neurons in a mouse model of Parkinson's disease.
Identifieur interne : 000763 ( PubMed/Corpus ); précédent : 000762; suivant : 000764MFGE8 does not orchestrate clearance of apoptotic neurons in a mouse model of Parkinson's disease.
Auteurs : Kiyoka Kinugawa ; Yann Monnet ; Lixia Lu ; Amaury J. Bekaert ; Clotilde Théry ; Ziad Mallat ; Etienne C. Hirsch ; Stéphane HunotSource :
- Neurobiology of disease [ 1095-953X ] ; 2013.
English descriptors
- KwdEn :
- Animals, Antigens, Surface (metabolism), Apoptosis (physiology), Astrocytes (metabolism), Brain (metabolism), Brain (pathology), Humans, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Milk Proteins (metabolism), Neurons (pathology), Parkinson Disease (metabolism), Parkinson Disease (pathology), Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction.
- MESH :
- chemical , metabolism : Antigens, Surface, Milk Proteins.
- metabolism : Astrocytes, Brain, Parkinson Disease.
- pathology : Brain, Neurons, Parkinson Disease.
- physiology : Apoptosis.
- Animals, Humans, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction.
Abstract
Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by a loss of dopaminergic neurons (DN) in the substantia nigra (SN). Several lines of evidence suggest that apoptotic cell death of DN is driven in part by non-cell autonomous mechanisms implicating microglial cells and inflammatory processes. Yet, how apoptotic DNs get removed by professional phagocytes and how this process modulates inflammatory processes are still unresolved issues. In this study, we investigated the role of MFGE8, a soluble factor involved in phagocytic recognition, in apoptotic DN clearance and neuroinflammation in PD. We report that glial expression of MFGE8 is enhanced in post-mortem PD brains compared to control individuals. Then, in vivo functional analysis of Mfge8 was assessed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD using wild-type (WT) and Mfge8-deficient mice. Neuropathological analysis consisted in evaluating (i) the loss of nigral DN and striatal DN terminals, (ii) the extent of glial cell activation and (iii) the number of apoptotic profiles. In vivo microglial phagocytic activity was further assessed by measuring the engulfment of apoptotic DN preloaded with fluorescent latex beads. Here we show that Mfge8 deficiency neither impact the phagocytic clearance of apoptotic bodies nor change the overall neuropathological parameters (DN cell loss and glial cell activation). In summary, our data argue that MFGE8 is not likely involved in the phagocytic clearance of neuronal debris associated with nigrostriatal pathway injury.
DOI: 10.1016/j.nbd.2012.11.010
PubMed: 23194669
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">MFGE8 does not orchestrate clearance of apoptotic neurons in a mouse model of Parkinson's disease.</title><author><name sortKey="Kinugawa, Kiyoka" sort="Kinugawa, Kiyoka" uniqKey="Kinugawa K" first="Kiyoka" last="Kinugawa">Kiyoka Kinugawa</name><affiliation><nlm:affiliation>CNRS, UMR 7225, Experimental Therapeutics of Neurodegeneration, F-75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Monnet, Yann" sort="Monnet, Yann" uniqKey="Monnet Y" first="Yann" last="Monnet">Yann Monnet</name></author><author><name sortKey="Lu, Lixia" sort="Lu, Lixia" uniqKey="Lu L" first="Lixia" last="Lu">Lixia Lu</name></author><author><name sortKey="Bekaert, Amaury J" sort="Bekaert, Amaury J" uniqKey="Bekaert A" first="Amaury J" last="Bekaert">Amaury J. Bekaert</name></author><author><name sortKey="Thery, Clotilde" sort="Thery, Clotilde" uniqKey="Thery C" first="Clotilde" last="Théry">Clotilde Théry</name></author><author><name sortKey="Mallat, Ziad" sort="Mallat, Ziad" uniqKey="Mallat Z" first="Ziad" last="Mallat">Ziad Mallat</name></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. Hirsch</name></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:23194669</idno><idno type="pmid">23194669</idno><idno type="doi">10.1016/j.nbd.2012.11.010</idno><idno type="wicri:Area/PubMed/Corpus">000763</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000763</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">MFGE8 does not orchestrate clearance of apoptotic neurons in a mouse model of Parkinson's disease.</title><author><name sortKey="Kinugawa, Kiyoka" sort="Kinugawa, Kiyoka" uniqKey="Kinugawa K" first="Kiyoka" last="Kinugawa">Kiyoka Kinugawa</name><affiliation><nlm:affiliation>CNRS, UMR 7225, Experimental Therapeutics of Neurodegeneration, F-75013 Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Monnet, Yann" sort="Monnet, Yann" uniqKey="Monnet Y" first="Yann" last="Monnet">Yann Monnet</name></author><author><name sortKey="Lu, Lixia" sort="Lu, Lixia" uniqKey="Lu L" first="Lixia" last="Lu">Lixia Lu</name></author><author><name sortKey="Bekaert, Amaury J" sort="Bekaert, Amaury J" uniqKey="Bekaert A" first="Amaury J" last="Bekaert">Amaury J. Bekaert</name></author><author><name sortKey="Thery, Clotilde" sort="Thery, Clotilde" uniqKey="Thery C" first="Clotilde" last="Théry">Clotilde Théry</name></author><author><name sortKey="Mallat, Ziad" sort="Mallat, Ziad" uniqKey="Mallat Z" first="Ziad" last="Mallat">Ziad Mallat</name></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C" last="Hirsch">Etienne C. Hirsch</name></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name></author></analytic><series><title level="j">Neurobiology of disease</title><idno type="eISSN">1095-953X</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antigens, Surface (metabolism)</term><term>Apoptosis (physiology)</term><term>Astrocytes (metabolism)</term><term>Brain (metabolism)</term><term>Brain (pathology)</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Milk Proteins (metabolism)</term><term>Neurons (pathology)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (pathology)</term><term>Real-Time Polymerase Chain Reaction</term><term>Reverse Transcriptase Polymerase Chain Reaction</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, Surface</term><term>Milk Proteins</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Astrocytes</term><term>Brain</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Brain</term><term>Neurons</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Apoptosis</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Real-Time Polymerase Chain Reaction</term><term>Reverse Transcriptase Polymerase Chain Reaction</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by a loss of dopaminergic neurons (DN) in the substantia nigra (SN). Several lines of evidence suggest that apoptotic cell death of DN is driven in part by non-cell autonomous mechanisms implicating microglial cells and inflammatory processes. Yet, how apoptotic DNs get removed by professional phagocytes and how this process modulates inflammatory processes are still unresolved issues. In this study, we investigated the role of MFGE8, a soluble factor involved in phagocytic recognition, in apoptotic DN clearance and neuroinflammation in PD. We report that glial expression of MFGE8 is enhanced in post-mortem PD brains compared to control individuals. Then, in vivo functional analysis of Mfge8 was assessed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD using wild-type (WT) and Mfge8-deficient mice. Neuropathological analysis consisted in evaluating (i) the loss of nigral DN and striatal DN terminals, (ii) the extent of glial cell activation and (iii) the number of apoptotic profiles. In vivo microglial phagocytic activity was further assessed by measuring the engulfment of apoptotic DN preloaded with fluorescent latex beads. Here we show that Mfge8 deficiency neither impact the phagocytic clearance of apoptotic bodies nor change the overall neuropathological parameters (DN cell loss and glial cell activation). In summary, our data argue that MFGE8 is not likely involved in the phagocytic clearance of neuronal debris associated with nigrostriatal pathway injury.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">23194669</PMID><DateCreated><Year>2013</Year><Month>01</Month><Day>28</Day></DateCreated><DateCompleted><Year>2013</Year><Month>07</Month><Day>24</Day></DateCompleted><DateRevised><Year>2013</Year><Month>01</Month><Day>28</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1095-953X</ISSN><JournalIssue CitedMedium="Internet"><Volume>51</Volume><PubDate><Year>2013</Year><Month>Mar</Month></PubDate></JournalIssue><Title>Neurobiology of disease</Title><ISOAbbreviation>Neurobiol. Dis.</ISOAbbreviation></Journal><ArticleTitle>MFGE8 does not orchestrate clearance of apoptotic neurons in a mouse model of Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>192-201</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1016/j.nbd.2012.11.010</ELocationID><ELocationID EIdType="pii" ValidYN="Y">S0969-9961(12)00373-7</ELocationID><Abstract><AbstractText>Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by a loss of dopaminergic neurons (DN) in the substantia nigra (SN). Several lines of evidence suggest that apoptotic cell death of DN is driven in part by non-cell autonomous mechanisms implicating microglial cells and inflammatory processes. Yet, how apoptotic DNs get removed by professional phagocytes and how this process modulates inflammatory processes are still unresolved issues. In this study, we investigated the role of MFGE8, a soluble factor involved in phagocytic recognition, in apoptotic DN clearance and neuroinflammation in PD. We report that glial expression of MFGE8 is enhanced in post-mortem PD brains compared to control individuals. Then, in vivo functional analysis of Mfge8 was assessed in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD using wild-type (WT) and Mfge8-deficient mice. Neuropathological analysis consisted in evaluating (i) the loss of nigral DN and striatal DN terminals, (ii) the extent of glial cell activation and (iii) the number of apoptotic profiles. In vivo microglial phagocytic activity was further assessed by measuring the engulfment of apoptotic DN preloaded with fluorescent latex beads. Here we show that Mfge8 deficiency neither impact the phagocytic clearance of apoptotic bodies nor change the overall neuropathological parameters (DN cell loss and glial cell activation). In summary, our data argue that MFGE8 is not likely involved in the phagocytic clearance of neuronal debris associated with nigrostriatal pathway injury.</AbstractText><CopyrightInformation>Copyright © 2012 Elsevier Inc. All rights reserved.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Kinugawa</LastName><ForeName>Kiyoka</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>CNRS, UMR 7225, Experimental Therapeutics of Neurodegeneration, F-75013 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Monnet</LastName><ForeName>Yann</ForeName><Initials>Y</Initials></Author><Author ValidYN="Y"><LastName>Lu</LastName><ForeName>Lixia</ForeName><Initials>L</Initials></Author><Author ValidYN="Y"><LastName>Bekaert</LastName><ForeName>Amaury J</ForeName><Initials>AJ</Initials></Author><Author ValidYN="Y"><LastName>Théry</LastName><ForeName>Clotilde</ForeName><Initials>C</Initials></Author><Author ValidYN="Y"><LastName>Mallat</LastName><ForeName>Ziad</ForeName><Initials>Z</Initials></Author><Author ValidYN="Y"><LastName>Hirsch</LastName><ForeName>Etienne C</ForeName><Initials>EC</Initials></Author><Author ValidYN="Y"><LastName>Hunot</LastName><ForeName>Stéphane</ForeName><Initials>S</Initials></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2012</Year><Month>11</Month><Day>27</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Neurobiol Dis</MedlineTA><NlmUniqueID>9500169</NlmUniqueID><ISSNLinking>0969-9961</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000954">Antigens, Surface</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C098942">MFGE8 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C490919">Mfge8 protein, 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