Journal article
Metal chaperones prevent zinc-mediated cognitive decline
PA Adlard, J Parncutt, V Lal, S James, D Hare, P Doble, DI Finkelstein, AI Bush
Neurobiology of Disease | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2015
Abstract
Zinc transporter-3 (ZnT3) protein is responsible for loading zinc into presynaptic vesicles and consequently controls the availability of zinc at the glutamatergic synapse. ZnT3 has been shown to decline with age and in Alzheimer's disease (AD) and is crucially involved in learning and memory. In this study, we utilised whole animal behavioural analyses in the ZnT3 KO mouse line, together with electrophysiological analysis of long-term potentiation in brain slices from ZnT3 KO mice, to show that metal chaperones (clioquinol, 30 mg/kg/day for 6 weeks) can prevent the age-dependent cognitive phenotype that characterises these animals. This likely occurs as a result of a homeostatic restoration..
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Funding Acknowledgements
We thank Milawaty Nurjono and Gulay Filiz for assistance with experiments. PAA, DIF and AIB are supported by the National Health and Medical Research Council. PM is also supported by the Australian Research Council. The 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. Parts of this research were undertaken on the X-ray Fluorescence Microscopy beamline at the Australian Synchrotron, Victoria, Australia.