19
IRUS TotalDownloads
Altmetric
Activated microglia do not increase 18 kDa translocator protein (TSPO) expression in the multiple sclerosis brain
File | Description | Size | Format | |
---|---|---|---|---|
glia.24052.pdf | Published version | 3.04 MB | Adobe PDF | View/Open |
Title: | Activated microglia do not increase 18 kDa translocator protein (TSPO) expression in the multiple sclerosis brain |
Authors: | Nutma, E Gebro, E Marzin, MC Van der Valk, P Matthews, PM Owen, DR Amor, S |
Item Type: | Journal Article |
Abstract: | To monitor innate immune responses in the CNS, the 18 kDa Translocator protein (TSPO) is a frequently used target for PET imaging. The frequent assumption that increased TSPO expression in the human CNS reflects pro-inflammatory activation of microglia has been extrapolated from rodent studies. However, TSPO expression does not increase in activated human microglia in vitro. Studies of multiple sclerosis (MS) lesions reveal that TSPO is not restricted to pro-inflammatory microglia/macrophages, but also present in homeostatic or reparative microglia. Here, we investigated quantitative relationships between TSPO expression and microglia/macrophage phenotypes in white matter and lesions of brains with MS pathology. In white matter from brains with no disease pathology, normal appearing white matter (NAWM), active MS lesions and chronic active lesion rims, over 95% of TSPO+ cells are microglia/macrophages. Homeostatic microglial markers in NAWM and control tissue are lost/reduced in active lesions and chronic active lesion rims, reflecting cell activation. Nevertheless, pixel analysis of TSPO+ cells (n = 12,225) revealed that TSPO expression per cell is no higher in active lesions and chronic active lesion rims (where myeloid cells are activated) relative to NAWM and control. This data suggests that whilst almost all the TSPO signal in active lesions, chronic active lesion rims, NAWM and control is associated with microglia/macrophages, their TSPO expression predominantly reflects cell density and not activation phenotype. This finding has implications for the interpretation of TSPO PET signal in MS and other CNS diseases, and further demonstrates the limitation of extrapolating TSPO biology from rodents to humans. |
Issue Date: | Oct-2021 |
Date of Acceptance: | 9-Jun-2021 |
URI: | http://hdl.handle.net/10044/1/90379 |
DOI: | 10.1002/glia.24052 |
ISSN: | 0894-1491 |
Publisher: | WILEY |
Start Page: | 2447 |
End Page: | 2458 |
Journal / Book Title: | GLIA |
Volume: | 69 |
Issue: | 10 |
Copyright Statement: | © 2021 The Authors. GLIA published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
Sponsor/Funder: | Medical Research Council (MRC) National Institute for Health Research UK DRI Ltd UK DRI Ltd Medical Research Council (MRC) |
Funder's Grant Number: | MR/N026934/1 RDA26 4050641385 DRI-DSI2020-001 MR/N008219/1 |
Keywords: | Science & Technology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology CD68 HLA-DR IBA-1 microglia multiple sclerosis P2ry12 TSPO PERIPHERAL BENZODIAZEPINE BINDING LESIONS WHITE PET LOCALIZATION INFLAMMATION MACROPHAGES PATHOLOGY DISEASE CD68 HLA-DR IBA-1 P2ry12 TSPO microglia multiple sclerosis Science & Technology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology CD68 HLA-DR IBA-1 microglia multiple sclerosis P2ry12 TSPO PERIPHERAL BENZODIAZEPINE BINDING LESIONS WHITE PET LOCALIZATION INFLAMMATION MACROPHAGES PATHOLOGY DISEASE Neurology & Neurosurgery 1109 Neurosciences |
Publication Status: | Published |
Online Publication Date: | 2021-06-19 |
Appears in Collections: | Faculty of Medicine Department of Brain Sciences |
This item is licensed under a Creative Commons License