Journal
NEUROSCIENCE
Volume 362, Issue -, Pages 141-151Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2017.08.023
Keywords
brain-iron; 6-OHDA; MRI; blood-brain barrier; microglia
Categories
Funding
- Swedish Research Council (VR-M grant) [09917]
- Ahlen Foundation
- Swedish Brain Foundation (Hjarnfonden)
- Umea University Medical Faculty Foundations
- Strategic Neuroscience Program Umea University-Karolinska Institute (StratNeuro)
- 7th Framework European Programme (Capacities) [FP7-REGPOT-2012-CT2012-31637-IMBRAIN]
- ACIISI [TESIS2015010082]
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Brain iron accumulation is a common feature shared by several neurodegenerative disorders including Parkinson's disease. However, what produces this accumulation of iron is still unknown. In this study, the 6-hydroxydopamine (6-OHDA) hemi-parkinsonian rat model was used to investigate abnormal iron accumulation in substantia nigra. We investigated three possible causes of iron accumulation; a compromised blood-brain barrier (BBB), abnormal expression of ferritin, and neuroinflammation. We identified alterations in the BBB subsequent to the injection of 6-OHDA using gadolinium-enhanced magnetic resonance imaging (MRI). Moreover, detection of extravasated IgG suggested that peripheral components are able to enter the brain through a leaky BBB. Presence of iron following dopamine cell degeneration was studied by MRI, which revealed hypointense signals in the substantia nigra. The presence of iron deposits was further validated in histological evaluations. Furthermore, iron inclusions were closely associated with active microglia and with increased levels of L-ferritin indicating a putative role for microglia and L-ferritin in brain iron accumulation and dopamine neurodegeneration. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
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