Journal Article

DZNE-2021-00190

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Attenuation of the extracellular matrix restores microglial activity during the early stage of amyloidosis.

Stoyanov, S. B. (First author)DZNE* ; Sun, W.DZNE* ; Düsedau, H. P. ; Cangalaya, C.DZNE* ; Choi, I.DZNE* ; Mirzapourdelavar, H.DZNE* ; Baidoe-Ansah, D.Extern* ; Kaushik, R.DZNE* ; Neumann, J. ; Dunay, I. R. ; Dityatev, A. (Last author)DZNE*

2021
Wiley-Liss Bognor Regis [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1002/glia.23894

Abstract: In the advanced stages of Alzheimer's disease (AD), microglia are transformed to an activated phenotype with thickened and retracted processes, migrate to the site of amyloid-beta (Aβ) plaques, and proliferate. In the early stages of AD, it is still poorly understood whether the microglial function is altered and which factors may regulate these changes. Here, we focused on studying microglia in the retrosplenial cortex (RSC) in 3- to 4-month-old 5xFAD mice as a transgenic mouse model of AD. At this age, there are neither Aβ plaques, nor activation of microglia, nor dysregulation in the expression of genes encoding major extracellular matrix (ECM) molecules or extracellular proteases in the RSC. Still, histochemical evaluation of the fine structure of neural ECM revealed increased levels of Wisteria floribunda agglutinin labeling in holes of perineuronal nets and changes in the perimeter of ECM barriers around the holes in 5xFAD mice. Two-photon vital microscopy demonstrated normal morphology and resting motility of microglia but strongly diminished number of microglial cells that migrated to the photolesion site in 5xFAD mice. Enzymatic digestion of ECM by chondroitinase ABC (ChABC) ameliorated this defect. Accordingly, the characterization of cell surface markers by flow cytometry demonstrated altered expression of microglial CD45. Moreover, ChABC treatment reduced the invasion of myeloid-derived mononuclear cells into the RSC of 5xFAD mice. Hence, the migration of both microglia and myeloid cells is altered during the early stages of amyloidosis and can be restored at least partially by the attenuation of the ECM.

Keyword(s): Alzheimer Disease (MeSH) ; Amyloid beta-Peptides (MeSH) ; Amyloidosis (MeSH) ; Animals (MeSH) ; Disease Models, Animal (MeSH) ; Extracellular Matrix (MeSH) ; Mice (MeSH) ; Mice, Transgenic (MeSH) ; Microglia (MeSH) ; Plaque, Amyloid (MeSH) ; Alzheimer's disease ; amyloidosis ; chondroitinase ABC ; extracellular matrix ; microglia ; neuroinflammation ; retrosplenial cortex

Note: ISSN 1098-1136 not unique: **3 hits**.

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Contributing Institute(s):

1. Molecular Neuroplasticity (AG Dityatev)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)

Appears in the scientific report 2021

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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