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.
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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.
| Type: | Article |
|---|---|
| Title: | CD206+/MHCII− macrophage accumulation at nerve injury site correlates with attenuation of allodynia in TASTPM mouse model of Alzheimer's disease |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bbih.2022.100548 |
| Publisher version: | https://doi.org/10.1016/j.bbih.2022.100548 |
| Language: | English |
| Additional information: | © 2022 The Authors. Published by Elsevier Inc. under a Creative Commons license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Neuropathic pain, Alzheimer's disease, Opioids, Sciatic nerve, Macrophage, Monocyte |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10166055 |
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