- Title
- Abrogation of type-I interferon signalling alters the microglial response to Aß1-42
- Creator
- Moore, Zachery; Mobilio, Frank; Walker, Frederick R.; Taylor, Juliet M.; Crack, Peter J.
- Relation
- Scientific reports Vol. 10, Issue 1, no. 3153
- Publisher Link
- http://dx.doi.org/10.1038/s41598-020-59917-0
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2020
- Description
- Neuroinflammation and accompanying microglial dysfunction are now appreciated to be involved in Alzheimer’s disease (AD) pathogenesis. Critical to the process of neuroinflammation are the type-I interferon (IFN) family of cytokines. Efforts to phenotypically characterize microglia within AD identify distinct populations associated with type-I IFN signalling, yet how this affects underlying microglial function is yet to be fully elucidated. Here we demonstrate that Aβ1–42 exposure increases bioactive levels of type-I IFN produced by primary microglia alongside increased expression of type-I IFN related genes. Primary microglia isolated from brains of APPswePS1ΔE9 mice with ablated type-I IFN signalling show an increased phagocytic ability to uptake FITC-Aβ1–42. Correlative assessment of plaque sizes in aged APPswePS1ΔE9 mice with abrogated type-I IFN signalling show unchanged deposition levels. Microglia from these mice did however show alterations in morphology. This data further highlights the role of type-I IFN signalling within microglia and identifies a role in phagocytosis. As such, targeting both microglial and global type-I IFN signalling presents as a novel therapeutic strategy for AD management.
- Subject
- cellular neuroscience; microglia; neuroinflammation; alzheimers disease
- Identifier
- http://hdl.handle.net/1959.13/1452714
- Identifier
- uon:44488
- Identifier
- ISSN:2045-2322
- Rights
- © The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. (https://creativecommons.org/licenses/by/4.0/).
- Language
- eng
- Full Text
- Reviewed
- Hits: 1540
- Visitors: 1680
- Downloads: 147
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | SOURCE1 | Publisher Version (open access) | 4 MB | Adobe Acrobat PDF | View Details Download |