eprintid: 10166055
rev_number: 6
eprint_status: archive
userid: 699
dir: disk0/10/16/60/55
datestamp: 2023-03-08 14:37:30
lastmod: 2023-03-08 14:37:30
status_changed: 2023-03-08 14:37:30
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Silva, Rita
creators_name: Sideris-Lampretsas, George
creators_name: Fox, Sarah
creators_name: Zeboudj, Lynda
creators_name: Malcangio, Marzia
title: CD206+/MHCII− macrophage accumulation at nerve injury site correlates with attenuation of allodynia in TASTPM mouse model of Alzheimer's disease
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: G02
keywords: Neuropathic pain, Alzheimer's disease, Opioids, Sciatic nerve, Macrophage, Monocyte
note: © 2022 The Authors. Published by Elsevier Inc. under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/).
abstract: Chronic pain is undertreated in people with Alzheimer's disease (AD) and better understanding of the underlying mechanisms of chronic pain in this neurodegenerative disease is essential. Neuropathic pain and AD share a significant involvement of the peripheral immune system. Therefore, we examined the development of nerve injury-induced allodynia in TASTPM (APPsweXPS1.M146V) mice and assessed monocytes/macrophages at injury site. TASTPM developed partial allodynia compared to WT at days 7, 14 and 21 days after injury, and showed complete allodynia only after treatment with naloxone methiodide, a peripheralized opioid receptor antagonist. Since macrophages are one of the sources of endogenous opioids in the periphery, we examined macrophage infiltration at injury site and observed that CD206+/MHCII− cells were more numerous in TASTPM than WT. Accordingly, circulating TASTPM Ly6Chigh (classical) monocytes, which are pro-inflammatory and infiltrate at the site of injury, were less abundant than in WT. In in vitro experiments, TASTPM bone marrow-derived macrophages showed efficient phagocytosis of myelin extracts containing amyloid precursor protein, acquired CD206+/MHCII− phenotype, upregulated mRNA expression of proenkephalin (PENK) and accumulated enkephalins in culture media. These data suggest that in TASTPM nerve-injured mice, infiltrating macrophages which derive from circulating monocytes and may contain amyloid fragments, acquire M2-like phenotype after myelin engulfment, and release enkephalins which are likely to inhibit nociceptive neuron activity via activation of opioid receptors.
date: 2022-12
date_type: published
publisher: Elsevier BV
official_url: https://doi.org/10.1016/j.bbih.2022.100548
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2008960
doi: 10.1016/j.bbih.2022.100548
lyricists_name: Sideris-Lampretsas, Georgios
lyricists_id: GSIDE10
actors_name: Sideris-Lampretsas, Georgios
actors_id: GSIDE10
actors_role: owner
full_text_status: public
publication: Brain, Behavior, & Immunity - Health
volume: 26
article_number: 100548
citation:        Silva, Rita;    Sideris-Lampretsas, George;    Fox, Sarah;    Zeboudj, Lynda;    Malcangio, Marzia;      (2022)    CD206+/MHCII− macrophage accumulation at nerve injury site correlates with attenuation of allodynia in TASTPM mouse model of Alzheimer's disease.                   Brain, Behavior, & Immunity - Health , 26     , Article 100548.  10.1016/j.bbih.2022.100548 <https://doi.org/10.1016/j.bbih.2022.100548>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10166055/1/1-s2.0-S2666354622001387-main.pdf