Myeloperoxidase-immunoreactive cells are significantly increased in brain areas affected by neurodegeneration in Parkinson’s and Alzheimer’s disease

Myeloperoxidase (MPO) is a key enzyme in inflammatory and degenerative processes, although conflicting reports have been presented concerning its expression in the brain. We studied the cellular localization of MPO and compared numbers of MPO cells in various brain regions between neurologically hea...

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Veröffentlicht in:Cell and tissue research 2017-09, Vol.369 (3), p.445-454
Hauptverfasser: Gellhaar, Sandra, Sunnemark, Dan, Eriksson, Håkan, Olson, Lars, Galter, Dagmar
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Sunnemark, Dan
Eriksson, Håkan
Olson, Lars
Galter, Dagmar
description Myeloperoxidase (MPO) is a key enzyme in inflammatory and degenerative processes, although conflicting reports have been presented concerning its expression in the brain. We studied the cellular localization of MPO and compared numbers of MPO cells in various brain regions between neurologically healthy individuals and patients with Parkinson’s disease (PD) or Alzheimer’s disease (AD; n  = 10–25). We also investigated two rodent PD models. MPO immunoreactivity (ir) was detected in monocytes, perivascular macrophages and amoeboid microglia in the human brain parenchyma, whereas no co-localization with glial fibrillary acidic protein (GFAP) ir was observed. In the midbrain, caudate and putamen, we found a significant increase of MPO-immunoreactive cells in PD compared with control brains, whereas in the cerebellum, no difference was apparent. MPO ir was detected neither in neurons nor in occasional small beta-amyloid-immunoreactive plaques in PD or control cases. In the frontal cortex of AD patients, we found significantly more MPO-immunoreactive cells compared with control cases, together with intense MPO ir in extracellular plaques. In the hippocampus of several AD cases, MPO-like ir was observed in some pyramidal neurons. Neither rapid dopamine depletion in the rat PD model, nor slow degeneration of dopamine neurons in MitoPark mice induced the expression of MPO ir in any brain region. MPO mRNA was not detectable with radioactive in situ hybridization in any human or rodent brain area, although myeloid cells from bone marrow displayed clear MPO signals. Our results indicate significant increases of MPO-immunoreactive cells in brain regions affected by neurodegeneration in PD and AD, supporting investigations of MPO inhibitors in novel treatment strategies.
doi_str_mv 10.1007/s00441-017-2626-8
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We studied the cellular localization of MPO and compared numbers of MPO cells in various brain regions between neurologically healthy individuals and patients with Parkinson’s disease (PD) or Alzheimer’s disease (AD; n  = 10–25). We also investigated two rodent PD models. MPO immunoreactivity (ir) was detected in monocytes, perivascular macrophages and amoeboid microglia in the human brain parenchyma, whereas no co-localization with glial fibrillary acidic protein (GFAP) ir was observed. In the midbrain, caudate and putamen, we found a significant increase of MPO-immunoreactive cells in PD compared with control brains, whereas in the cerebellum, no difference was apparent. MPO ir was detected neither in neurons nor in occasional small beta-amyloid-immunoreactive plaques in PD or control cases. In the frontal cortex of AD patients, we found significantly more MPO-immunoreactive cells compared with control cases, together with intense MPO ir in extracellular plaques. In the hippocampus of several AD cases, MPO-like ir was observed in some pyramidal neurons. Neither rapid dopamine depletion in the rat PD model, nor slow degeneration of dopamine neurons in MitoPark mice induced the expression of MPO ir in any brain region. MPO mRNA was not detectable with radioactive in situ hybridization in any human or rodent brain area, although myeloid cells from bone marrow displayed clear MPO signals. 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enzymology</topic><topic>Alzheimer Disease - pathology</topic><topic>Alzheimer's disease</topic><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Bone marrow</topic><topic>Brain</topic><topic>Brain - enzymology</topic><topic>Brain - pathology</topic><topic>Cellular biology</topic><topic>Cerebellum</topic><topic>Cortex (frontal)</topic><topic>Dopamine</topic><topic>Enzymes</topic><topic>Female</topic><topic>frontal lobe</topic><topic>Glial fibrillary acidic protein</topic><topic>hippocampus</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Immunoreactivity</topic><topic>in situ hybridization</topic><topic>Inflammation</topic><topic>Localization</topic><topic>Macrophages</topic><topic>Male</topic><topic>Mesencephalon</topic><topic>messenger RNA</topic><topic>mice</topic><topic>Microglia</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Monocytes</topic><topic>Movement disorders</topic><topic>mRNA</topic><topic>Myeloid cells</topic><topic>myeloperoxidase</topic><topic>Nerve Degeneration - 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In the hippocampus of several AD cases, MPO-like ir was observed in some pyramidal neurons. Neither rapid dopamine depletion in the rat PD model, nor slow degeneration of dopamine neurons in MitoPark mice induced the expression of MPO ir in any brain region. MPO mRNA was not detectable with radioactive in situ hybridization in any human or rodent brain area, although myeloid cells from bone marrow displayed clear MPO signals. Our results indicate significant increases of MPO-immunoreactive cells in brain regions affected by neurodegeneration in PD and AD, supporting investigations of MPO inhibitors in novel treatment strategies.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>28466093</pmid><doi>10.1007/s00441-017-2626-8</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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1432-0878
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source MEDLINE; Springer Nature - Complete Springer Journals; SWEPUB Freely available online
subjects Advertising executives
Aged
Aged, 80 and over
Alzheimer disease
Alzheimer Disease - enzymology
Alzheimer Disease - pathology
Alzheimer's disease
Analysis
Animal models
Animals
Biomedical and Life Sciences
Biomedicine
Bone marrow
Brain
Brain - enzymology
Brain - pathology
Cellular biology
Cerebellum
Cortex (frontal)
Dopamine
Enzymes
Female
frontal lobe
Glial fibrillary acidic protein
hippocampus
Human Genetics
Humans
Immunoreactivity
in situ hybridization
Inflammation
Localization
Macrophages
Male
Mesencephalon
messenger RNA
mice
Microglia
Middle Aged
Molecular Medicine
Monocytes
Movement disorders
mRNA
Myeloid cells
myeloperoxidase
Nerve Degeneration - enzymology
Nerve Degeneration - pathology
Neurodegeneration
Neurodegenerative diseases
neuroglia
Neurons
Parenchyma
parenchyma (animal tissue)
Parkinson disease
Parkinson Disease - enzymology
Parkinson Disease - pathology
Parkinson's disease
patients
Peroxidase
Peroxidase - metabolism
Plaques
Proteomics
Putamen
rats
Rats, Sprague-Dawley
Regular
Regular Article
β-Amyloid
title Myeloperoxidase-immunoreactive cells are significantly increased in brain areas affected by neurodegeneration in Parkinson’s and Alzheimer’s disease
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