title: Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging.
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.
authors: 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.
authors: Feng
authors: F
authors: Tian
authors: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Wenlong
authors: W
authors: Yang
authors: 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 Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors: Daniel A
authors: DA
authors: Mordes
authors: 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.
authors: Jin-Yuan
authors: JY
authors: Wang
authors: Department of Neurology, University of Massachusetts Memorial Medical Center, Worcester, Massachusetts 01655, USA.
authors: Johnny S
authors: JS
authors: Salameh
authors: 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.
authors: Joanie
authors: J
authors: Mok
authors: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Jeannie
authors: J
authors: Chew
authors: Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA.
authors: Aarti
authors: A
authors: Sharma
authors: 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.
authors: Ester
authors: E
authors: Leno-Duran
authors: 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.
authors: Satomi
authors: S
authors: Suzuki-Uematsu
authors: 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.
authors: Naoki
authors: N
authors: Suzuki
authors: 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.
authors: Steve S
authors: SS
authors: Han
authors: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.|Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.
authors: Fa-Ke
authors: FK
authors: Lu
authors: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: Minbiao
authors: M
authors: Ji
authors: 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.
authors: Rosanna
authors: R
authors: Zhang
authors: 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.
authors: Yue
authors: Y
authors: Liu
authors: 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.
authors: Jack
authors: J
authors: Strominger
authors: Department of Neurology, Columbia University Medical Center, New York, New York 10032, USA.
authors: Neil A
authors: NA
authors: Shneider
authors: Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA.
authors: Leonard
authors: L
authors: Petrucelli
authors: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors: X Sunney
authors: XS
authors: Xie
authors: 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.
authors: Kevin
authors: K
authors: Eggan
mesh_terms: D000465:Algorithms; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology*; D000818:Animals; D000900:Anti-Bacterial Agents; D016477:Artifacts; D003198:Computer Simulation; D018450:Disease Progression; D004576:Electromyography; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008055:Lipids / Q000737:chemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008911:Minocycline / Q000737:chemistry; D009046:Motor Neurons / Q000473:pathology; D009186:Myelin Sheath / Q000737:chemistry; D009410:Nerve Degeneration / Q000473:pathology*; D010525:Peripheral Nerves / Q000473:pathology*; D012584:Sciatic Nerve / Q000473:pathology; D013059:Spectrum Analysis, Raman; D000072105:Superoxide Dismutase-1 / Q000235:genetics; D019076:Transgenes
chemical_list: D000900:Anti-Bacterial Agents; D008055:Lipids; C000606290:SOD1 protein, human; C000606291:Sod1 protein, mouse; D000072105:Superoxide Dismutase-1; D008911:Minocycline