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The Amyloid-beta rich CNS environment alters myeloid cell functionality independent of their origin.

Authors :
Drost N
Houtman J
Cseresnyés Z
Niesner R
Rinnenthal JL
Miller KR
Prokop S
Heppner FL
Source :
Scientific reports [Sci Rep] 2020 Apr 28; Vol. 10 (1), pp. 7152. Date of Electronic Publication: 2020 Apr 28.
Publication Year :
2020

Abstract

Microglia, the innate immune cells of the central nervous system (CNS) survey their surroundings with their cytoplasmic processes, phagocytose debris and rapidly respond to injury. These functions are affected by the presence of beta-Amyloid (Aβ) deposits, hallmark lesions of Alzheimer's disease (AD). We recently demonstrated that exchanging functionally altered endogenous microglia with peripheral myeloid cells did not change Aβ-burden in a mouse model mimicking aspects of AD at baseline, and only mildly reduced Aβ plaques upon stimulation. To better characterize these different myeloid cell populations, we used long-term in vivo 2-photon microscopy to compare morphology and basic functional parameters of brain populating peripherally-derived myeloid cells and endogenous microglia. While peripherally-derived myeloid cells exhibited increased process movement in the non-diseased brain, the Aβ rich environment in an AD-like mouse model, which induced an alteration of surveillance functions in endogenous microglia, also restricted functional characteristics and response to CNS injury of newly recruited peripherally-derived myeloid cells. Our data demonstrate that the Aβ rich brain environment alters the functional characteristics of endogenous microglia as well as newly recruited peripheral myeloid cells, which has implications for the role of myeloid cells in disease and the utilization of these cells in Alzheimer's disease therapy.

Details

Language :
English
ISSN :
2045-2322
Volume :
10
Issue :
1
Database :
MEDLINE
Journal :
Scientific reports
Publication Type :
Academic Journal
Accession number :
32346002
Full Text :
https://doi.org/10.1038/s41598-020-63989-3