Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role

WALLER, Rachel, WOODROOFE, Nicola, WHARTON, Stephen B., INCE, Paul G., FRANCESE, Simona, HEATH, Paul R., CUDZICH-MADRY, A, THOMAS, Ruth, ROUNDING, Natalie, SHARRACK, Basil and SIMPSON, Julie E. (2016). Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role. Journal of Neuroimmunology, 299, 139-146.

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Abstract

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of the central nervous system (CNS). White matter lesions in MS are surrounded by areas of non-demyelinated normal appearing white matter (NAWM) with complex pathology, including blood brain barrier dysfunction, axonal damage and glial activation. Astrocytes, the most abundant cell type within the CNS, may respond and/or contribute to lesion pathogenesis. We aimed to characterise the transcriptomic profile of astrocytes in NAWM to determine whether specific glial changes exist in the NAWM which contribute to lesion development or prevent disease progression. Astrocytes were isolated from control and NAWM by laser capture microdissection (LCM), using glial fibrillary acidic protein (GFAP) as a marker, and the astrocyte transcriptome determined using microarray analysis. 452 genes were significantly differentially expressed (208 up-regulated and 244 down-regulated, FC ≥ 1.5 and p-value ≤ 0.05). Within the NAWM, astrocytes were associated with significant upregulation of genes involved in the control of iron homeostasis (including metallothionein-1 and -2, ferritin light chain and transferrin), oxidative stress responses, the immune response and neurotrophic support. These findings suggest a neuroprotective role of astrocytes in the NAWM in MS

Item Type:	Article
Research Institute, Centre or Group - Does NOT include content added after October 2018:	Biomedical Research Centre
Identification Number:	https://doi.org/10.1016/j.jneuroim.2016.09.010
Page Range:	139-146
Depositing User:	Margaret Boot
Date Deposited:	20 Oct 2016 11:50
Last Modified:	18 Mar 2021 04:10
URI:	https://shura.shu.ac.uk/id/eprint/13853

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