期刊
JOURNAL OF NEUROSCIENCE
卷 32, 期 1, 页码 133-142出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4846-11.2012
关键词
-
资金
- J. David Gladstone Institutes
- Taube-Koret Center for Huntington's Disease Research
- Natural Sciences and Engineering Research Council, Canada
- National Institutes of Health [P30NS065780]
- Medical Research Council [MR/J003832/1] Funding Source: researchfish
- MRC [MR/J003832/1] Funding Source: UKRI
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-gamma 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据