Unravelling and Exploiting Astrocyte Dysfunction in Huntington's Disease

Baljit S Khakh; Vahri Beaumont; Roger Cachope; Ignacio Munoz-Sanjuan; Steven A Goldman; Rosemarie Grantyn

doi:10.1016/j.tins.2017.05.002

Unravelling and Exploiting Astrocyte Dysfunction in Huntington's Disease

Trends Neurosci. 2017 Jul;40(7):422-437. doi: 10.1016/j.tins.2017.05.002. Epub 2017 May 31.

Authors

Baljit S Khakh¹, Vahri Beaumont², Roger Cachope², Ignacio Munoz-Sanjuan², Steven A Goldman³, Rosemarie Grantyn⁴

Affiliations

¹ Department of Physiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USA; Neurobiology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095-1751, USA. Electronic address: bkhakh@mednet.ucla.edu.
² CHDI Management/CHDI Foundation, 6080 Center Drive, Los Angeles, CA 90045, USA.
³ Center for Translational Neuromedicine, University of Rochester, Rochester, NY 14642, USA; Center for Neuroscience, University of Copenhagen, 2200 Copenhagen N, Denmark.
⁴ Exzellenzcluster NeuroCure & Abt. Experimentelle Neurologie, Charité - Universitätsmedizin Berlin, Robert-Koch-Platz 4, D-10115 Berlin, Germany.

Abstract

Astrocytes are abundant within mature neural circuits and are involved in brain disorders. Here, we summarize our current understanding of astrocytes and Huntington's disease (HD), with a focus on correlative and causative dysfunctions of ion homeostasis, calcium signaling, and neurotransmitter clearance, as well as on the use of transplanted astrocytes to produce therapeutic benefit in mouse models of HD. Overall, the data suggest that astrocyte dysfunction is an important contributor to the onset and progression of some HD symptoms in mice. Additional exploration of astrocytes in HD mouse models and humans is needed and may provide new therapeutic opportunities to explore in conjunction with neuronal rescue and repair strategies.

Keywords: EAAT2; GAT3; GCaMP; GLT1; HD; KCNJ10; Kir4.1; astrocyte; calcium.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Astrocytes / pathology
Astrocytes / physiology*
Astrocytes / transplantation*
Humans
Huntington Disease / pathology
Huntington Disease / physiopathology*
Huntington Disease / therapy*

Abstract

Publication types

MeSH terms

Grants and funding