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Nat Commun. 2016 Oct 31;7:13283. doi: 10.1038/ncomms13283.

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

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Department of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Department of Molecular and Cellular Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts 02138, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts 01655, USA.
Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.


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.

[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

X.S.X. is a cofounder of Invenio Imaging, a start-up for SRS microscopy. The remaining authors declare no competing financial interests.

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