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The Role of Astrocytes in Huntington’s Disease

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Pathological Potential of Neuroglia

Abstract

Huntington’s disease (HD) is a progressive autosomal dominant neurodegenerative disorder characterized by psychiatric disturbances, cognitive impairment and choreiform movements. It is caused by a repeat expansion in the gene encoding the widely expressed protein HTT. This protein is present throughout the nervous system in neuronal and non-neuronal cell types. The mutant HTT (mHTT) protein has been implicated in multiple cellular processes. To date, however, no single mechanism has been shown to be the primary mechanism that leads to neuronal dysfunction and death. Instead, it is believed that multiple mechanisms together may contribute to HD pathogenesis. At present, there is no effective neuroprotective treatment for HD. Although mHTT is found in astrocytes, most of the focus to date has been on understanding processes that may be dysfunctional in neurons. Nonetheless, there is substantial evidence for abnormal astrocytes in HD. In this chapter we present a review of the current understanding of astrocyte involvement in HD. We describe observations made in HD patients concerning morphological and molecular changes in astrocytes as disease progresses. Additionally, we describe the recapitulation of some of the phenotypes observed in HD patients in various mouse models expressing the mHTT protein. Together, the data from patients and the mouse models strongly implicate astrocyte-specific mechanisms as players in the pathogenesis of HD.

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Abbreviations

CAG:

Cytosine-adenosine-guanine

CPN:

Cortical pyramidal neurons

CT:

Computed tomography

EAAT2:

Excitatory amino acid transporter 2

GFAP:

Glial fibrillary associated protein

GLT-1:

Glutamate transporter 1

GS:

Glutamine synthetase

HD:

Huntington’s disease

Hdh:

Huntington disease homologue

HTT:

Huntingtin

MAP2:

Microtubule associated protein

MRI:

Magnetic resonance imaging

MSN:

Medium spiny neurons

PC:

Pyruvate carboxylase

PET:

Positron emission tomography

polyQ:

Polyglutamine

TCA:

Tricarboxylic acid cycle

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Acknowledgements

The authors’ work is supported by grants from the Dixon Family Foundation, the Hereditary Disease Foundation and the National Institutes of Health.

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  1. Department of Neurology, Center for Neurodegeneration and Experimental Therapeutics, University of Alabama at Birmingham, 1719 6th Ave South, CIRC 525b1, 35294, Birmingham, AL, USA

    Michelle Gray

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Correspondence to Michelle Gray .

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  1. Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

    Vladimir Parpura

  2. Faculty of Life Sciences, The University of Manchester, Manchester, United Kingdom

    Alexei Verkhratsky

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Gray, M. (2014). The Role of Astrocytes in Huntington’s Disease. In: Parpura, V., Verkhratsky, A. (eds) Pathological Potential of Neuroglia. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0974-2_10

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