Progressive Cognitive Deficit, Motor Impairment and Striatal Pathology in a Transgenic Huntington Disease Monkey Model from Infancy to Adulthood

Authors

Anthony W. S. Chan, Emory University School of Medicine
Jie Jiang, Emory University School of Medicine
Yiju Chen, Emory University School of Medicine
Chunxia Li, Emory University
Melinda S. Prucha, Emory University School of Medicine
Yijuan Hu, Emory University School of Public Health
Tim Chi, Emory University
Sean Moran, Emory University
Tayeb Rahim, Emory University
Shihua Li, Emory University School of Medicine
Xiaojiang Li, Emory University School of Medicine
Stuart M. Zola, Emory University School of Medicine
Claudia M. Testa, Virginia Commonwealth UniversityFollow
Hui Mao, Emory University School of Medicine
Rosa Villalba, Emory University
Yoland Smith, Emory University
Xiaodong Zhang, Emory University
Jocelyne Bachevalier, Emory University

Document Type

Article

Original Publication Date

2015

Journal/Book/Conference Title

PLoS ONE

Volume

10

Issue

5

DOI of Original Publication

10.1371/journal.pone.0122335

Comments

Originally published at http://dx.doi.org/10.1371/journal.pone.0122335

Date of Submission

November 2015

Abstract

One of the roadblocks to developing effective therapeutics for Huntington disease (HD) is the lack of animal models that develop progressive clinical traits comparable to those seen in patients. Here we report a longitudinal study that encompasses cognitive and motor assessment, and neuroimaging of a group of transgenic HD and control monkeys from infancy to adulthood. Along with progressive cognitive and motor impairment, neuroimaging revealed a progressive reduction in striatal volume. Magnetic resonance spectroscopy at 48 months of age revealed a decrease of N-acetylaspartate (NAA), further suggesting neuronal damage/loss in the striatum. Postmortem neuropathological analyses revealed significant neuronal loss in the striatum. Our results indicate that HD monkeys share similar disease patterns with HD patients, making them potentially suitable as a preclinical HD animal model.

Rights

Chan, A. W. S., Jiang, J., & Chen, Y., et al. Progressive Cognitive Deficit, Motor Impairment and Striatal Pathology in a Transgenic Huntington Disease Monkey Model from Infancy to Adulthood. PLoS ONE, 10, e0122335. Copyright © 2015 Chan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Is Part Of

VCU Neurology Publications