Lithium suppression of tau induces brain iron accumulation and neurodegeneration

P Lei; S Ayton; AT Appukuttan; S Moon; JA Duce; I Volitakis; R Cherny; SJ Wood; M Greenough; G Berger; C Pantelis; P McGorry; A Yung; DI Finkelstein; AI Bush

Journal article

Lithium suppression of tau induces brain iron accumulation and neurodegeneration

P Lei, S Ayton, AT Appukuttan, S Moon, JA Duce, I Volitakis, R Cherny, SJ Wood, M Greenough, G Berger, C Pantelis, P McGorry, A Yung, DI Finkelstein, AI Bush

MOLECULAR PSYCHIATRY | NATURE PUBLISHING GROUP | Published : 2017

DOI: 10.1038/mp.2016.96

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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 featu..

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University of Melbourne Researchers

Ashley Bush Author Florey Department of Neuroscience and Mental Health

Christos Pantelis Author Psychiatry

James Duce Author Florey Department of Neuroscience and Mental Health

Scott Ayton Author Florey Department of Neuroscience and Mental Health

Stephen Wood Author Centre for Youth Mental Health

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Grants

Awarded by National Natural Science Foundation of China

Awarded by NHMRC Australia Fellowship

Awarded by NHMRC Senior Principal Research Fellowship

Awarded by NHMRC Project Grant

Awarded by NHMRC Program Grants

Funding Acknowledgements

We thank A Sedjahtera, L Lam, L Gunawan, L Bray and K Wikhe for technical assistance. We also acknowledge L Phillips and B Nelson for their contributions in lithium human trial. This study was supported by funds from the Australian Research Council, the National Health & Medical Research Council (NHMRC) of Australia, the Cooperative Research Center for Mental Health, Alzheimer's Australia Dementia Research Foundation and National Natural Science Foundation of China (81571236). A Bush was supported by a NHMRC Australia Fellowship (AF79) and a NHMRC Senior Principal Research Fellowship (1103703). C Pantelis was supported by a NHMRC Senior Principal Research Fellowship (628386 and 1105825). The imaging work on lithium was supported by NHMRC Project Grant (145627) and NHMRC Program Grants (350241 and 566529). P McGorry currently receives research support from NHMRC of Australia, the Colonial Foundation and NARSAD. Florey Institute of Neuroscience and Mental Health acknowledges the strong support from the Victorian Government and in particular the funding from the Operational Infrastructure Support Grant.