Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging

Feng Tian, Wenlong Yang, Daniel A. Mordes, Jin-Yuan Wang, Johnny S. Salameh, Joanie Mok, Jeannie Chew, Aarti Sharma, Ester Leno-Duran, Satomi Suzuki-Uematsu, Naoki Suzuki, Steve S. Han, Fa-Ke Lu, Minbiao Ji, Rosanna Zhang, Yue Liu, Jack Strominger, Neil A. Shneider, Leonard Petrucelli, X. Sunney Xie () and Kevin Eggan ()
Additional contact information
Feng Tian: Harvard Stem Cell Institute, Harvard University
Wenlong Yang: Harvard University
Daniel A. Mordes: Harvard Stem Cell Institute, Harvard University
Jin-Yuan Wang: Harvard Stem Cell Institute, Harvard University
Johnny S. Salameh: University of Massachusetts Memorial Medical Center
Joanie Mok: Harvard Stem Cell Institute, Harvard University
Jeannie Chew: Mayo Clinic
Aarti Sharma: Columbia University Medical Center
Ester Leno-Duran: Harvard Stem Cell Institute, Harvard University
Satomi Suzuki-Uematsu: Harvard Stem Cell Institute, Harvard University
Naoki Suzuki: Harvard Stem Cell Institute, Harvard University
Steve S. Han: Harvard Stem Cell Institute, Harvard University
Fa-Ke Lu: Harvard University
Minbiao Ji: Harvard University
Rosanna Zhang: Harvard Stem Cell Institute, Harvard University
Yue Liu: Harvard Stem Cell Institute, Harvard University
Jack Strominger: Harvard Stem Cell Institute, Harvard University
Neil A. Shneider: Columbia University Medical Center
Leonard Petrucelli: Mayo Clinic
X. Sunney Xie: Harvard University
Kevin Eggan: Harvard Stem Cell Institute, Harvard University

Nature Communications, 2016, vol. 7, issue 1, 1-15

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms13283

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