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Articles, Neurobiology of Disease

Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington's Disease

Wanda Kwan, Anna Magnusson, Austin Chou, Anthony Adame, Monica J. Carson, Shinichi Kohsaka, Eliezer Masliah, Thomas Möller, Richard Ransohoff, Sarah J. Tabrizi, Maria Björkqvist and Paul J. Muchowski
Journal of Neuroscience 4 January 2012, 32 (1) 133-142; DOI: https://doi.org/10.1523/JNEUROSCI.4846-11.2012
Wanda Kwan
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Anna Magnusson
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Austin Chou
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Anthony Adame
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Monica J. Carson
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Shinichi Kohsaka
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Eliezer Masliah
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Thomas Möller
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Richard Ransohoff
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Sarah J. Tabrizi
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Maria Björkqvist
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Paul J. Muchowski
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Abstract

Huntington's disease (HD) is caused by an expanded polyglutamine tract in the protein huntingtin (htt). Although HD has historically been viewed as a brain-specific disease, htt is expressed ubiquitously, and recent studies indicate that mutant htt might cause changes to the immune system that could contribute to pathogenesis. Monocytes from HD patients and mouse models are hyperactive in response to stimulation, and increased levels of inflammatory cytokines and chemokines are found in pre-manifest patients that correlate with pathogenesis. In this study, wild-type (WT) bone marrow cells were transplanted into two lethally irradiated transgenic mouse models of HD that ubiquitously express full-length htt (YAC128 and BACHD mice). Bone marrow transplantation partially attenuated hypokinetic and motor deficits in HD mice. Increased levels of synapses in the cortex were found in HD mice that received bone marrow transplants. Importantly, serum levels of interleukin-6, interleukin-10, CXC chemokine ligand 1, and interferon-γ were significantly higher in HD than WT mice but were normalized in mice that received a bone marrow transplant. These results suggest that immune cell dysfunction might be an important modifier of pathogenesis in HD.

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The Journal of Neuroscience: 32 (1)
Journal of Neuroscience
Vol. 32, Issue 1
4 Jan 2012
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Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington's Disease
Wanda Kwan, Anna Magnusson, Austin Chou, Anthony Adame, Monica J. Carson, Shinichi Kohsaka, Eliezer Masliah, Thomas Möller, Richard Ransohoff, Sarah J. Tabrizi, Maria Björkqvist, Paul J. Muchowski
Journal of Neuroscience 4 January 2012, 32 (1) 133-142; DOI: 10.1523/JNEUROSCI.4846-11.2012

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Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington's Disease
Wanda Kwan, Anna Magnusson, Austin Chou, Anthony Adame, Monica J. Carson, Shinichi Kohsaka, Eliezer Masliah, Thomas Möller, Richard Ransohoff, Sarah J. Tabrizi, Maria Björkqvist, Paul J. Muchowski
Journal of Neuroscience 4 January 2012, 32 (1) 133-142; DOI: 10.1523/JNEUROSCI.4846-11.2012
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