Florey Department of Neuroscience and Mental Health - Research Publications

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Brain Zinc Deficiency Exacerbates Cognitive Decline in the R6/1 Model of Huntington's Disease.

Ayton, S ; Lei, P ; Appukuttan, AT ; Renoir, T ; Foliaki, S ; Chen, F ; Adlard, PA ; Hannan, AJ ; Bush, AI (Springer Nature, 2020-01)

There is currently no disease-modifying treatment for Huntington's disease (HD), which is characterized by chorea motor impairment and cognitive decline. The zinc ionophore, PBT2, was previously shown to improve the phenotype of a HD mouse model and reported efficacy in certain cognitive tests in a phase II clinical trial in HD. Here we report that zinc deficiency is a feature of the hippocampus and cortex in the R6/1 mouse model of HD. Low cortical zinc has been shown to induce cognitive impairment, and indeed, dietary restriction of zinc in R6/1 mice was associated with cognitive impairment in the Y-maze, an exacerbated hippocampal long-term potentiation (LTP) deficit and reduction of AMPA receptors (and not other glutamatergic receptors). These data reveal the importance of zinc in maintaining brain function in HD.