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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Brain iron dysregulation and the risk of ageing white matter lesions
NeuroMolecular Medicine, Volume 13, No. 4, Year 2011
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Description
White matter lesions (WML) or leukoaraiosis is a major feature in cerebral imaging of older people, and their prevalence increases with age. The clinical effects of WML vary with the main impairment being detected in the cognitive functions, increased risk of severe depression and motor impairment. Although vascular comorbidities have been found to be the main changes in these brains, increased production of reactive oxygen species (ROS) could represent a risk factor for these lesions with elemental iron being a potential factor for ROS production. This study focuses on changes in iron, iron-regulating proteins and RNA expression of iron metabolism genes. Three groups of samples were used: WML, normal areas from lesional WM [NAWM (L)] as disease control and normal WM from control brains [NAWM(C)]. Ferric iron staining was undertaken using known Perl's reaction. Immunohistochemistry (IHC) of white matter for cerulo-plasmin (Cp), haemochromatosis (HFE) and transferrin receptor (TfR) was done. Cellular localization of HFE and Cp was performed using dual-antibody IHC. Whole-genome RNA was extracted from WML, NAWM (L) and NAWM(C), and QPCR for HFE, TF, TfR, ceruloplasmin, ferritin and ferroportin was performed. Ferric iron staining shows increased diffuse iron staining among WML, followed by NAWM (L) and the least group being NAWM(C). IHC shows increased HFE and CP expression in lesional WM, while TfR shows no changes among the groups. HFE colocalized with vascular endothelium and microglia in WML and control samples, while Cp colocalized with microglia and some expression was shown by astrocytes. The mRNA expression using QPCR suggests a pattern that favours decreased intracellular iron influx, increased ferrous oxidation and increased iron export from the cells. Iron metabolism seems to be changed in brains with WML, increased elemental iron in these brains and in turn increased production of free oxidative radicals could represent a potentiating factor for the development of ageing WML. © Springer Science+Business Media, LLC 2011.
Authors & Co-Authors
Gebril, Ola H.
Egypt, Giza
National Research Centre
United Kingdom, Sheffield
The University of Sheffield
Simpson, J. E.
United Kingdom, Sheffield
The University of Sheffield
Kirby, Janine
United Kingdom, Sheffield
The University of Sheffield
Brayne, C. E.G.
United Kingdom, Cambridge
Cambridge Institute of Public Health
Ince, Paul G.
United Kingdom, Sheffield
The University of Sheffield
Statistics
Citations: 20
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1007/s12017-011-8161-y
ISSN:
15351084
e-ISSN:
15591174
Research Areas
Mental Health
Study Design
Cross Sectional Study