Bone marrow transplantation confers modest benefits in mouse models of Huntington's disease.
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.
Biomedical Sciences Program, Gladstone Institute of Neurological Disease, University of California, San Francisco, San Francisco, California 94158, USA.
Wanda
W
Kwan
Anna
A
Magnusson
Austin
A
Chou
Anthony
A
Adame
Monica J
MJ
Carson
Shinichi
S
Kohsaka
Eliezer
E
Masliah
Thomas
T
Möller
Richard
R
Ransohoff
Sarah J
SJ
Tabrizi
Maria
M
Björkqvist
Paul J
PJ
Muchowski
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000503:physiopathology / Q000628:therapy*; D001854:Bone Marrow Cells / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D007165:Immunosuppression Therapy / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic