Age Influences Microglial Activation After Cuprizone-Induced Demyelination
Multiple sclerosis (MS) is a chronic inflammatory CNS disease, which causes demyelinated lesions and damages white and gray matter regions. Aging is a significant factor in the progression of MS, and microglia, the immune cells of the CNS tissue, play an important role in all disease stages. During...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-09-01
|
Series: | Frontiers in Aging Neuroscience |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2018.00278/full |
id |
doaj-1c8220c990884ce6bfa7f952c83582cd |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Barbara Klein Barbara Klein Heike Mrowetz Heike Mrowetz Conor Michael Barker Conor Michael Barker Simona Lange Simona Lange Francisco J. Rivera Francisco J. Rivera Francisco J. Rivera Francisco J. Rivera Ludwig Aigner Ludwig Aigner |
spellingShingle |
Barbara Klein Barbara Klein Heike Mrowetz Heike Mrowetz Conor Michael Barker Conor Michael Barker Simona Lange Simona Lange Francisco J. Rivera Francisco J. Rivera Francisco J. Rivera Francisco J. Rivera Ludwig Aigner Ludwig Aigner Age Influences Microglial Activation After Cuprizone-Induced Demyelination Frontiers in Aging Neuroscience microglia aging demyelination cuprizone hippocampus corpus callosum |
author_facet |
Barbara Klein Barbara Klein Heike Mrowetz Heike Mrowetz Conor Michael Barker Conor Michael Barker Simona Lange Simona Lange Francisco J. Rivera Francisco J. Rivera Francisco J. Rivera Francisco J. Rivera Ludwig Aigner Ludwig Aigner |
author_sort |
Barbara Klein |
title |
Age Influences Microglial Activation After Cuprizone-Induced Demyelination |
title_short |
Age Influences Microglial Activation After Cuprizone-Induced Demyelination |
title_full |
Age Influences Microglial Activation After Cuprizone-Induced Demyelination |
title_fullStr |
Age Influences Microglial Activation After Cuprizone-Induced Demyelination |
title_full_unstemmed |
Age Influences Microglial Activation After Cuprizone-Induced Demyelination |
title_sort |
age influences microglial activation after cuprizone-induced demyelination |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Aging Neuroscience |
issn |
1663-4365 |
publishDate |
2018-09-01 |
description |
Multiple sclerosis (MS) is a chronic inflammatory CNS disease, which causes demyelinated lesions and damages white and gray matter regions. Aging is a significant factor in the progression of MS, and microglia, the immune cells of the CNS tissue, play an important role in all disease stages. During aging, microglia are functionally altered. These age-related changes probably already begin early and might influence the progression of CNS pathologies. The aim of the present study was to investigate whether microglia in the middle-aged CNS already react differently to demyelination. For this purpose, several microglia markers (ionized calcium binding adaptor molecule 1 (Iba-1), P2RY12, F4/80, CD68, major histocompatibility complex II (MHCII), macrophage receptor with collagenous structure (Marco), Translocator protein 18 kD (TSPO), CD206, and CD163) were analyzed in the acute cuprizone demyelination model in young (2-month-old) and middle-aged (10-month-old) mice. In addition, microglial proliferation was quantified using double-labeling with proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU), which was injected with the onset of remyelination. To compare age-related microglial changes during de- and remyelination in both gray and white matter, the hilus of the dorsal hippocampal dentate gyrus (DG) and the splenium of the corpus callosum (CC) were analyzed in parallel. Age-related changes in microglia of healthy controls were more pronounced in the analyzed gray matter region (higher levels of F4/80 and Marco as well as lower expression of CD68 in middle-aged mice). During de- and remyelination, a stronger increase of the microglial markers Iba-1, CD68 and TSPO was observed in the splenium of the younger groups. There was a significant reduction of P2RY12 during demyelination, however, this was age- and region-dependent. The induction of the anti-inflammatory markers CD206 and CD163 was stronger in the middle-aged group, but also differed between the two analyzed regions. De- and remyelination led to a significant increase in PCNA+ microglia only in young groups within the white matter region. The number of BrdU+ microglia was not changed during de- or remyelination. These results clearly show that microglia are already altered during middle-age and also react differently to CNS demyelination, however, this is highly region-dependent. |
topic |
microglia aging demyelination cuprizone hippocampus corpus callosum |
url |
https://www.frontiersin.org/article/10.3389/fnagi.2018.00278/full |
work_keys_str_mv |
AT barbaraklein ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT barbaraklein ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT heikemrowetz ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT heikemrowetz ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT conormichaelbarker ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT conormichaelbarker ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT simonalange ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT simonalange ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT franciscojrivera ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT franciscojrivera ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT franciscojrivera ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT franciscojrivera ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT ludwigaigner ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination AT ludwigaigner ageinfluencesmicroglialactivationaftercuprizoneinduceddemyelination |
_version_ |
1725809937436639232 |
spelling |
doaj-1c8220c990884ce6bfa7f952c83582cd2020-11-24T22:09:56ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652018-09-011010.3389/fnagi.2018.00278381190Age Influences Microglial Activation After Cuprizone-Induced DemyelinationBarbara Klein0Barbara Klein1Heike Mrowetz2Heike Mrowetz3Conor Michael Barker4Conor Michael Barker5Simona Lange6Simona Lange7Francisco J. Rivera8Francisco J. Rivera9Francisco J. Rivera10Francisco J. Rivera11Ludwig Aigner12Ludwig Aigner13Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, AustriaInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, AustriaInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, AustriaInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, AustriaInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, AustriaLaboratory of Stem Cells and Neuroregeneration, Institute of Anatomy, Histology and Pathology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, ChileCenter for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia, ChileInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, Salzburg, AustriaSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, AustriaMultiple sclerosis (MS) is a chronic inflammatory CNS disease, which causes demyelinated lesions and damages white and gray matter regions. Aging is a significant factor in the progression of MS, and microglia, the immune cells of the CNS tissue, play an important role in all disease stages. During aging, microglia are functionally altered. These age-related changes probably already begin early and might influence the progression of CNS pathologies. The aim of the present study was to investigate whether microglia in the middle-aged CNS already react differently to demyelination. For this purpose, several microglia markers (ionized calcium binding adaptor molecule 1 (Iba-1), P2RY12, F4/80, CD68, major histocompatibility complex II (MHCII), macrophage receptor with collagenous structure (Marco), Translocator protein 18 kD (TSPO), CD206, and CD163) were analyzed in the acute cuprizone demyelination model in young (2-month-old) and middle-aged (10-month-old) mice. In addition, microglial proliferation was quantified using double-labeling with proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU), which was injected with the onset of remyelination. To compare age-related microglial changes during de- and remyelination in both gray and white matter, the hilus of the dorsal hippocampal dentate gyrus (DG) and the splenium of the corpus callosum (CC) were analyzed in parallel. Age-related changes in microglia of healthy controls were more pronounced in the analyzed gray matter region (higher levels of F4/80 and Marco as well as lower expression of CD68 in middle-aged mice). During de- and remyelination, a stronger increase of the microglial markers Iba-1, CD68 and TSPO was observed in the splenium of the younger groups. There was a significant reduction of P2RY12 during demyelination, however, this was age- and region-dependent. The induction of the anti-inflammatory markers CD206 and CD163 was stronger in the middle-aged group, but also differed between the two analyzed regions. De- and remyelination led to a significant increase in PCNA+ microglia only in young groups within the white matter region. The number of BrdU+ microglia was not changed during de- or remyelination. These results clearly show that microglia are already altered during middle-age and also react differently to CNS demyelination, however, this is highly region-dependent.https://www.frontiersin.org/article/10.3389/fnagi.2018.00278/fullmicrogliaagingdemyelinationcuprizonehippocampuscorpus callosum |