Human Glia Can Both Induce and Rescue Aspects of Disease Phenotype in Huntington Disease

Authors

Abdellatif Benraiss
Su Wang
Stephanie Herrlinger
Xiaojie Li
Devin Chandler-Militello
Jian Kang, New York Medical CollegeFollow
Steven Goldman
Martha S. Windrem
Ignacio Munoz-Sanjuan
Maiken Nedergaard
Steven A. Goldman

First Page

11758

Last Page

11758

Document Type

Article

Publication Date

6-7-2016

Department

Cell Biology and Anatomy

Abstract

The causal contribution of glial pathology to Huntington disease (HD) has not been heavily explored. To define the contribution of glia to HD, we established human HD glial chimeras by neonatally engrafting immunodeficient mice with mutant huntingtin (mHTT)-expressing human glial progenitor cells (hGPCs), derived from either human embryonic stem cells or mHTT-transduced fetal hGPCs. Here we show that mHTT glia can impart disease phenotype to normal mice, since mice engrafted intrastriatally with mHTT hGPCs exhibit worse motor performance than controls, and striatal neurons in mHTT glial chimeras are hyperexcitable. Conversely, normal glia can ameliorate disease phenotype in transgenic HD mice, as striatal transplantation of normal glia rescues aspects of electrophysiological and behavioural phenotype, restores interstitial potassium homeostasis, slows disease progression and extends survival in R6/2 HD mice. These observations suggest a causal role for glia in HD, and further suggest a cell-based strategy for disease amelioration in this disorder.

Comments

Please see the work itself for the complete list of authors.

Recommended Citation

Benraiss, A., Wang, S., Herrlinger, S., Li, X., Chandler-Militello, D., Mauceri, J., et al. (2016). Human glia can both induce and rescue aspects of disease phenotype in huntington disease. Nature Communications, 7, Art. No.: 11758. doi:10.1038/ncomms11758

Publisher's Statement

Originally published in Nature Communications. Licensed under CC-BY 4.0. https://doi.org/10.1038/ncomms11758