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