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; Kevin Eggan

doi:10.1038/ncomms13283

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

Neuroscience

Research output: Contribution to journal › Article › peer-review

48 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 language	English (US)
Article number	13283
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms13283
State	Published - 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

Tian, F, Yang, W, Mordes, DA, Wang, JY, Salameh, JS, Mok, J, Chew, J, Sharma, A, Leno-Duran, E, Suzuki-Uematsu, S, Suzuki, N, Han, SS, Lu, FK, Ji, M, Zhang, R, Liu, Y, Strominger, J, Shneider, NA, Petrucelli, L, Xie, XS & Eggan, K 2016, 'Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging', Nature communications, vol. 7, 13283. https://doi.org/10.1038/ncomms13283

@article{50671b19942f4c43b8c2be6ca1773820,

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.",

author = "Feng Tian and Wenlong Yang and Mordes, {Daniel A.} and Wang, {Jin Yuan} and Salameh, {Johnny S.} and Joanie Mok and Jeannie Chew and Aarti Sharma and Ester Leno-Duran and Satomi Suzuki-Uematsu and Naoki Suzuki and Han, {Steve S.} and Lu, {Fa Ke} and Minbiao Ji and Rosanna Zhang and Yue Liu and Jack Strominger and Shneider, {Neil A.} and Leonard Petrucelli and Xie, {X. Sunney} and Kevin Eggan",

note = "Funding Information: We thank P. Arlotta, A. Cohen, F. Engert and J. Lichtman for informative suggestions on this work. We also thank A. Huang for the discussion on spectral reconstruction and S. Oh for the help on SRS signal measurement. This work was supported by the Howard Hughes Medical Institute, Target ALS, NINDS grant RO1NS01NS089742 to KE and National Institute of Health/National Institute of Biomedical Imaging and Bioengineering (Award #: 5R01EB010244). D.A.M. was supported by the Massachusetts Alzheimer's Disease Research Center (NIA P50 AG005134) and NCI 5T32CA009216-34. N.S. was a 2011 Lilly Scientific Fellow and received grant from The Mochida Memorial Foundation for Medical and Pharmaceutical Research. N.A.S and A.S. were supported by the National Institute of Neurological Disorders and Stroke (NINDS) (Award#: R01NS07377). This work was supported by the National Institutes of Health/National Institute on Aging (P50AG016574 (L.P.)), National Institutes of Health/National Institute of Neurological Disorders and Stroke (R21NS084528 (L.P.), R01NS088689 (L.P.), R01NS063964 (L.P.); R01NS077402 (L.P.); P01NS084974 (L.P.)), National Institute of Environmental Health Services (R01ES20395 (L.P.)), Mayo Clinic Foundation (L.P.), Mayo Graduate School (J.C.), ALS Association (L.P.) and Robert Packard Center for ALS Research at Johns Hopkins (L.P.), Target ALS (L.P.). Publisher Copyright: {\textcopyright} 2016 The Author(s).",

year = "2016",

month = oct,

day = "31",

doi = "10.1038/ncomms13283",

language = "English (US)",

volume = "7",

journal = "Nature Communications",

issn = "2041-1723",

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TY - JOUR

T1 - Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging

AU - Tian, Feng

AU - Yang, Wenlong

AU - Mordes, Daniel A.

AU - Wang, Jin Yuan

AU - Salameh, Johnny S.

AU - Mok, Joanie

AU - Chew, Jeannie

AU - Sharma, Aarti

AU - Leno-Duran, Ester

AU - Suzuki-Uematsu, Satomi

AU - Suzuki, Naoki

AU - Han, Steve S.

AU - Lu, Fa Ke

AU - Ji, Minbiao

AU - Zhang, Rosanna

AU - Liu, Yue

AU - Strominger, Jack

AU - Shneider, Neil A.

AU - Petrucelli, Leonard

AU - Xie, X. Sunney

AU - Eggan, Kevin

N1 - Funding Information: We thank P. Arlotta, A. Cohen, F. Engert and J. Lichtman for informative suggestions on this work. We also thank A. Huang for the discussion on spectral reconstruction and S. Oh for the help on SRS signal measurement. This work was supported by the Howard Hughes Medical Institute, Target ALS, NINDS grant RO1NS01NS089742 to KE and National Institute of Health/National Institute of Biomedical Imaging and Bioengineering (Award #: 5R01EB010244). D.A.M. was supported by the Massachusetts Alzheimer's Disease Research Center (NIA P50 AG005134) and NCI 5T32CA009216-34. N.S. was a 2011 Lilly Scientific Fellow and received grant from The Mochida Memorial Foundation for Medical and Pharmaceutical Research. N.A.S and A.S. were supported by the National Institute of Neurological Disorders and Stroke (NINDS) (Award#: R01NS07377). This work was supported by the National Institutes of Health/National Institute on Aging (P50AG016574 (L.P.)), National Institutes of Health/National Institute of Neurological Disorders and Stroke (R21NS084528 (L.P.), R01NS088689 (L.P.), R01NS063964 (L.P.); R01NS077402 (L.P.); P01NS084974 (L.P.)), National Institute of Environmental Health Services (R01ES20395 (L.P.)), Mayo Clinic Foundation (L.P.), Mayo Graduate School (J.C.), ALS Association (L.P.) and Robert Packard Center for ALS Research at Johns Hopkins (L.P.), Target ALS (L.P.). Publisher Copyright: © 2016 The Author(s).

PY - 2016/10/31

Y1 - 2016/10/31

N2 - 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.

AB - 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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JO - Nature Communications

JF - Nature Communications

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

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