Lei, P, Ayton, S, Appukuttan, AT et al. (12 more authors) (2017) Lithium suppression of tau induces brain iron accumulation and neurodegeneration. Molecular Psychiatry, 22 (3). pp. 396-406. ISSN 1359-4184
Abstract
Lithium is a first-line therapy for bipolar affective disorder. However, various adverse effects, including a Parkinson-like hand tremor, often limit its use. The understanding of the neurobiological basis of these side effects is still very limited. Nigral iron elevation is also a feature of Parkinsonian degeneration that may be related to soluble tau reduction. We found that magnetic resonance imaging T2 relaxation time changes in subjects commenced on lithium therapy were consistent with iron elevation. In mice, lithium treatment lowers brain tau levels and increases nigral and cortical iron elevation that is closely associated with neurodegeneration, cognitive loss and parkinsonian features. In neuronal cultures lithium attenuates iron efflux by lowering tau protein that traffics amyloid precursor protein to facilitate iron efflux. Thus, tau- and amyloid protein precursor-knockout mice were protected against lithium-induced iron elevation and neurotoxicity. These findings challenge the appropriateness of lithium as a potential treatment for disorders where brain iron is elevated (for example, Alzheimer’s disease), and may explain lithium-associated motor symptoms in susceptible patients.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016, Macmillan Publishers Limited. This is an author produced version of a paper published in Molecular Psychiatry. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Sep 2016 13:47 |
Last Modified: | 05 Nov 2017 15:24 |
Published Version: | https://doi.org/10.1038/mp.2016.96 |
Status: | Published |
Publisher: | Nature Publishing Group |
Identification Number: | 10.1038/mp.2016.96 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:104131 |