期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms13283
关键词
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资金
- Howard Hughes Medical Institute
- Target ALS
- NINDS [RO1NS01NS089742, R01NS07377]
- National Institute of Health/National Institute of Biomedical Imaging and Bioengineering [5R01EB010244]
- Massachusetts Alzheimer's Disease Research Center [NIA P50 AG005134]
- NCI [5T32CA009216-34]
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- National Institutes of Health/National Institute on Aging [P50AG016574]
- National Institutes of Health/National Institute of Neurological Disorders and Stroke [R21NS084528, R01NS088689, R01NS063964, R01NS077402, P01NS084974]
- National Institute of Environmental Health Services [R01ES20395]
- Mayo Clinic Foundation
- Mayo Graduate School
- ALS Association
- Robert Packard Center for ALS Research at Johns Hopkins
- Grants-in-Aid for Scientific Research [15H05667] Funding Source: KAKEN
The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics.
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