title: Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role.
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.
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Waller
authors.affiliation: Biomolecular Sciences Research Centre, Sheffield Hallam University, UK.
authors.forename: M Nicola
authors.initials: MN
authors.lastname: Woodroofe
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Wharton
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, UK.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Ince
authors.affiliation: Biomolecular Sciences Research Centre, Sheffield Hallam University, UK.
authors.forename: Simona
authors.initials: S
authors.lastname: Francese
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Heath
authors.affiliation: Biomolecular Sciences Research Centre, Sheffield Hallam University, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Cudzich-Madry
authors.affiliation: Biomolecular Sciences Research Centre, Sheffield Hallam University, UK.
authors.forename: Ruth H
authors.initials: RH
authors.lastname: Thomas
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, UK.
authors.forename: Natalie
authors.initials: N
authors.lastname: Rounding
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, UK; Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK.
authors.forename: Basil
authors.initials: B
authors.lastname: Sharrack
authors.affiliation: Sheffield Institute for Translational Neuroscience, University of Sheffield, UK. Electronic address: julie.simpson@sheffield.ac.uk.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Simpson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001253:Astrocytes / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D061346:Laser Capture Microdissection / Q000379:methods; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000502:physiology; D059467:Transcriptome / Q000502:physiology*; D066127:White Matter / Q000502:physiology*
keywords: Astrocyte; Microarray; Multiple sclerosis; Neuroprotection; Normal appearing white matter