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Lookup NU author(s): Professor Fiona MatthewsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.White matter lesions (WML) are a common feature of the ageing brain associated with cognitive impairment. The gene expression profiles of periventricular lesions (PVL, n = 7) and radiologically-normal-appearing (control) periventricular white matter cases (n = 11) obtained from the Cognitive Function and Ageing Study (CFAS) neuropathology cohort were interrogated using microarray analysis and NanoString to identify novel mechanisms potentially underlying their formation. Histological characterisation of control white matter cases identified a subgroup (n = 4) which contained high levels of MHC-II immunoreactive microglia, and were classified as “pre-lesional.” Microarray analysis identified 2256 significantly differentially-expressed genes (p ≤ 0.05, FC ≥ 1.2) in PVL compared to non-lesional control white matter (1378 upregulated and 878 downregulated); 2649 significantly differentially-expressed genes in “pre-lesional” cases compared to PVL (1390 upregulated and 1259 downregulated); and 2398 significantly differentially-expressed genes in “pre-lesional” versus non-lesional control cases (1527 upregulated and 871 downregulated). Whilst histological evaluation of a single marker (MHC-II) implicates immune-activated microglia in lesion pathology, transcriptomic analysis indicates significant downregulation of a number of activated microglial markers and suggests established PVL are part of a continuous spectrum of white matter injury. The gene expression profile of “pre-lesional” periventricular white matter suggests upregulation of several signalling pathways may be a neuroprotective response to prevent the pathogenesis of PVL.
Author(s): Fadul MM, Heath PR, Cooper-Knock J, Kurz JM, Al-Azzawi HA, Ali Z, Smith T, Matthews FE, Brayne C, Wharton SB, Simpson JE
Publication type: Article
Publication status: Published
Journal: International Journal of Molecular Sciences
Online publication date: 25/10/2020
Acceptance date: 23/10/2020
Date deposited: 09/11/2020
ISSN (print): 1661-6596
ISSN (electronic): 1422-0067
Publisher: MDPI AG
PubMed id: 33113879
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