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

ABSTRACT: 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.

SUBMITTER: Ayton S

PROVIDER: S-EPMC7007468 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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

Ayton Scott S Lei Peng P Appukuttan Ambili T AT Renoir Thibault T Foliaki Simote S Chen Feng F Adlard Paul A PA Hannan Anthony J AJ Bush Ashley I AI

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20200101 1

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 impair ...[more]

PMID: 31520307

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