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

Kwan, Wanda; Magnusson-Lind, Anna LU ; Chou, Austin; Adame, Anthony; Carson, Monica J; Kohsaka, Shinichi; Masliah, Eliezer; Möller, Thomas; Ransohoff, Richard and Tabrizi, Sarah J, et al. (2012) In The Journal of neuroscience : the official journal of the Society for Neuroscience 32(1). p.133-142
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... (More)
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. (Less)
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published
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The Journal of neuroscience : the official journal of the Society for Neuroscience
volume
32
issue
1
pages
133 - 142
publisher
Society for Neuroscience
external identifiers
  • wos:000299119700013
  • pmid:22219276
  • scopus:84855920796
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.4846-11.2012
language
English
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yes
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b9fe37c5-bbfd-4655-9653-a323d3ad8b70 (old id 2336680)
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http://www.ncbi.nlm.nih.gov/pubmed/22219276?dopt=Abstract
date added to LUP
2012-02-01 19:42:20
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2017-10-01 04:15:23
@article{b9fe37c5-bbfd-4655-9653-a323d3ad8b70,
  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.},
  author       = {Kwan, Wanda and Magnusson-Lind, Anna and Chou, Austin and Adame, Anthony and Carson, Monica J and Kohsaka, Shinichi and Masliah, Eliezer and Möller, Thomas and Ransohoff, Richard and Tabrizi, Sarah J and Björkqvist, Maria and Muchowski, Paul J},
  issn         = {1529-2401},
  language     = {eng},
  number       = {1},
  pages        = {133--142},
  publisher    = {Society for Neuroscience},
  series       = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
  title        = {Bone Marrow Transplantation Confers Modest Benefits in Mouse Models of Huntington's Disease.},
  url          = {http://dx.doi.org/10.1523/JNEUROSCI.4846-11.2012},
  volume       = {32},
  year         = {2012},
}