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 XieKevin Eggan

Research output: Contribution to journalArticle

38 Scopus citations

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.

Original languageEnglish (US)
Article number13283
JournalNature communications
Volume7
DOIs
StatePublished - Oct 31 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Tian, F., Yang, W., Mordes, D. A., Wang, J. Y., Salameh, J. S., Mok, J., Chew, J., Sharma, A., Leno-Duran, E., Suzuki-Uematsu, S., Suzuki, N., Han, S. S., Lu, F. K., Ji, M., Zhang, R., Liu, Y., Strominger, J., Shneider, N. A., Petrucelli, L., ... Eggan, K. (2016). Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging. Nature communications, 7, [13283]. https://doi.org/10.1038/ncomms13283