Elsevier

Neurotherapeutics

Volume 17, Issue 1, January 2020, Pages 243-251
Neurotherapeutics

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

https://doi.org/10.1007/s13311-019-00785-6Get rights and content
Under an Elsevier user license
open archive

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.

Key Words

Huntington's disease
zinc
cognition
animal model

Cited by (0)