Iron deficiency in parkinsonism: region-specific iron dysregulation in Parkinson's disease and multiple system atrophy.
Identifieur interne : 000D50 ( Main/Exploration ); précédent : 000D49; suivant : 000D51Iron deficiency in parkinsonism: region-specific iron dysregulation in Parkinson's disease and multiple system atrophy.
Auteurs : Naomi P. Visanji [Canada] ; Joanna F. Collingwood ; Mary E. Finnegan ; Anurag Tandon ; Emily House ; Lili-Naz HazratiSource :
- Journal of Parkinson's disease [ 1877-718X ] ; 2013.
English descriptors
- KwdEn :
- Aged, Brain (metabolism), Brain Chemistry, Case-Control Studies, Cation Transport Proteins (metabolism), Female, Ferritins (metabolism), Humans, Iron (deficiency), Iron (metabolism), Magnetometry (methods), Male, Microglia (chemistry), Microglia (metabolism), Middle Aged, Multiple System Atrophy (complications), Multiple System Atrophy (metabolism), Parkinson Disease (complications), Parkinson Disease (metabolism), Spectrophotometry, Atomic (methods).
- MESH :
- chemical , deficiency : Iron.
- chemical , metabolism : Cation Transport Proteins, Ferritins, Iron.
- chemistry : Microglia.
- complications : Multiple System Atrophy, Parkinson Disease.
- metabolism : Brain, Microglia, Multiple System Atrophy, Parkinson Disease.
- methods : Magnetometry, Spectrophotometry, Atomic.
- Aged, Brain Chemistry, Case-Control Studies, Female, Humans, Male, Middle Aged.
Abstract
Alpha synuclein pathology is widespread and found in diverse cell types in multiple system atrophy (MSA) as compared to Parkinson's disease (PD). The reason for this differential distribution is unknown. Regional differences in the distribution of iron are associated with neurodegenerative diseases, and here we characterize the relationship between iron homeostasis proteins and regional concentration, distribution and form of iron in MSA and PD. In PD substantia nigra, tissue iron and expression of the iron export protein ferroportin increased, while the iron storage protein ferritin expression was unchanged. In the basis pontis of MSA cases, increased total iron concentration coupled with a disproportionate increase in ferritin in dysmorphic microglia and a reduction in ferroportin expression. This is supported by isothermal remanent magnetisation evidence consistent with elevated concentrations of ferritin-bound iron in MSA basis pontis. Conventional opinion holds that excess iron is involved in neurodegeneration. Our data support that this may be the case in PD. While region-specific changes in iron are evident in both PD and MSA, the mechanisms of iron dysregulation appear quite distinct, with a failure to export iron from the MSA basis pontis coupling with significant intracellular accumulation of ferritin iron. This pattern also occurs, to a lesser extent, in the MSA putamen. Despite the excess tissue iron, the manner of iron dysregulation in MSA is reminiscent of changes in anemia of chronic disease, and our preliminary data, coupled with the widespread pathology and involvement of multiple cell types, may evidence a deficit in bioavailabile iron.
DOI: 10.3233/JPD-130197
PubMed: 24113558
Affiliations:
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Collingwood</name></author><author><name sortKey="Finnegan, Mary E" sort="Finnegan, Mary E" uniqKey="Finnegan M" first="Mary E" last="Finnegan">Mary E. Finnegan</name></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name></author><author><name sortKey="House, Emily" sort="House, Emily" uniqKey="House E" first="Emily" last="House">Emily House</name></author><author><name sortKey="Hazrati, Lili Naz" sort="Hazrati, Lili Naz" uniqKey="Hazrati L" first="Lili-Naz" last="Hazrati">Lili-Naz Hazrati</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2013">2013</date><idno type="RBID">pubmed:24113558</idno><idno type="pmid">24113558</idno><idno type="doi">10.3233/JPD-130197</idno><idno type="wicri:Area/PubMed/Corpus">000984</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000984</idno><idno type="wicri:Area/PubMed/Curation">000984</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000984</idno><idno type="wicri:Area/PubMed/Checkpoint">000984</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000984</idno><idno type="wicri:Area/Ncbi/Merge">001587</idno><idno type="wicri:Area/Ncbi/Curation">001587</idno><idno type="wicri:Area/Ncbi/Checkpoint">001587</idno><idno type="wicri:Area/Main/Merge">000D61</idno><idno type="wicri:Area/Main/Curation">000D50</idno><idno type="wicri:Area/Main/Exploration">000D50</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Iron deficiency in parkinsonism: region-specific iron dysregulation in Parkinson's disease and multiple system atrophy.</title><author><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P" last="Visanji">Naomi P. Visanji</name><affiliation wicri:level="1"><nlm:affiliation>Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, Toronto, ON, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, Toronto, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Collingwood, Joanna F" sort="Collingwood, Joanna F" uniqKey="Collingwood J" first="Joanna F" last="Collingwood">Joanna F. Collingwood</name></author><author><name sortKey="Finnegan, Mary E" sort="Finnegan, Mary E" uniqKey="Finnegan M" first="Mary E" last="Finnegan">Mary E. Finnegan</name></author><author><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name></author><author><name sortKey="House, Emily" sort="House, Emily" uniqKey="House E" first="Emily" last="House">Emily House</name></author><author><name sortKey="Hazrati, Lili Naz" sort="Hazrati, Lili Naz" uniqKey="Hazrati L" first="Lili-Naz" last="Hazrati">Lili-Naz Hazrati</name></author></analytic><series><title level="j">Journal of Parkinson's disease</title><idno type="eISSN">1877-718X</idno><imprint><date when="2013" type="published">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Brain (metabolism)</term><term>Brain Chemistry</term><term>Case-Control Studies</term><term>Cation Transport Proteins (metabolism)</term><term>Female</term><term>Ferritins (metabolism)</term><term>Humans</term><term>Iron (deficiency)</term><term>Iron (metabolism)</term><term>Magnetometry (methods)</term><term>Male</term><term>Microglia (chemistry)</term><term>Microglia (metabolism)</term><term>Middle Aged</term><term>Multiple System Atrophy (complications)</term><term>Multiple System Atrophy (metabolism)</term><term>Parkinson Disease (complications)</term><term>Parkinson Disease (metabolism)</term><term>Spectrophotometry, Atomic (methods)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="deficiency" xml:lang="en"><term>Iron</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Cation Transport Proteins</term><term>Ferritins</term><term>Iron</term></keywords><keywords scheme="MESH" qualifier="chemistry" xml:lang="en"><term>Microglia</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Multiple System Atrophy</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Microglia</term><term>Multiple System Atrophy</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Magnetometry</term><term>Spectrophotometry, Atomic</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Brain Chemistry</term><term>Case-Control Studies</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Alpha synuclein pathology is widespread and found in diverse cell types in multiple system atrophy (MSA) as compared to Parkinson's disease (PD). The reason for this differential distribution is unknown. Regional differences in the distribution of iron are associated with neurodegenerative diseases, and here we characterize the relationship between iron homeostasis proteins and regional concentration, distribution and form of iron in MSA and PD. In PD substantia nigra, tissue iron and expression of the iron export protein ferroportin increased, while the iron storage protein ferritin expression was unchanged. In the basis pontis of MSA cases, increased total iron concentration coupled with a disproportionate increase in ferritin in dysmorphic microglia and a reduction in ferroportin expression. This is supported by isothermal remanent magnetisation evidence consistent with elevated concentrations of ferritin-bound iron in MSA basis pontis. Conventional opinion holds that excess iron is involved in neurodegeneration. Our data support that this may be the case in PD. While region-specific changes in iron are evident in both PD and MSA, the mechanisms of iron dysregulation appear quite distinct, with a failure to export iron from the MSA basis pontis coupling with significant intracellular accumulation of ferritin iron. This pattern also occurs, to a lesser extent, in the MSA putamen. Despite the excess tissue iron, the manner of iron dysregulation in MSA is reminiscent of changes in anemia of chronic disease, and our preliminary data, coupled with the widespread pathology and involvement of multiple cell types, may evidence a deficit in bioavailabile iron.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Collingwood, Joanna F" sort="Collingwood, Joanna F" uniqKey="Collingwood J" first="Joanna F" last="Collingwood">Joanna F. Collingwood</name><name sortKey="Finnegan, Mary E" sort="Finnegan, Mary E" uniqKey="Finnegan M" first="Mary E" last="Finnegan">Mary E. Finnegan</name><name sortKey="Hazrati, Lili Naz" sort="Hazrati, Lili Naz" uniqKey="Hazrati L" first="Lili-Naz" last="Hazrati">Lili-Naz Hazrati</name><name sortKey="House, Emily" sort="House, Emily" uniqKey="House E" first="Emily" last="House">Emily House</name><name sortKey="Tandon, Anurag" sort="Tandon, Anurag" uniqKey="Tandon A" first="Anurag" last="Tandon">Anurag Tandon</name></noCountry><country name="Canada"><noRegion><name sortKey="Visanji, Naomi P" sort="Visanji, Naomi P" uniqKey="Visanji N" first="Naomi P" last="Visanji">Naomi P. Visanji</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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