Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration
Discovery of molecular mechanisms and chemical compounds that enhance neuronal regeneration can lead to development of therapeutics to combat nervous system injuries and neurodegenerative diseases. By combining high-throughput microfluidics and femtosecond laser microsurgery, we demonstrate for the...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences
2012
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| Online Access: | http://hdl.handle.net/1721.1/73171 https://orcid.org/0000-0002-4612-1962 |
| _version_ | 1826253198358216704 |
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| author | Gilleland, Cody Lee Rohde, Christopher Benjamin Samara, Chrysanthi Yanik, Mehmet Fatih Haggarty, Stephen J. |
| author2 | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science |
| author_facet | Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Gilleland, Cody Lee Rohde, Christopher Benjamin Samara, Chrysanthi Yanik, Mehmet Fatih Haggarty, Stephen J. |
| author_sort | Gilleland, Cody Lee |
| collection | MIT |
| description | Discovery of molecular mechanisms and chemical compounds that enhance neuronal regeneration can lead to development of therapeutics to combat nervous system injuries and neurodegenerative diseases. By combining high-throughput microfluidics and femtosecond laser microsurgery, we demonstrate for the first time large-scale in vivo screens for identification of compounds that affect neurite regeneration. We performed thousands of microsurgeries at single-axon precision in the nematode Caenorhabditis elegans at a rate of 20 seconds per animal. Following surgeries, we exposed the animals to a hand-curated library of approximately one hundred small molecules and identified chemicals that significantly alter neurite regeneration. In particular, we found that the PKC kinase inhibitor staurosporine strongly modulates regeneration in a concentration- and neuronal type-specific manner. Two structurally unrelated PKC inhibitors produce similar effects. We further show that regeneration is significantly enhanced by the PKC activator prostratin. |
| first_indexed | 2024-09-23T16:37:56Z |
| format | Article |
| id | mit-1721.1/73171 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:37:56Z |
| publishDate | 2012 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | mit-1721.1/731712022-09-29T20:27:27Z Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration Gilleland, Cody Lee Rohde, Christopher Benjamin Samara, Chrysanthi Yanik, Mehmet Fatih Haggarty, Stephen J. Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Gilleland, Cody Lee Rohde, Christopher Benjamin Samara, Chrysanthi Yanik, Mehmet Fatih Discovery of molecular mechanisms and chemical compounds that enhance neuronal regeneration can lead to development of therapeutics to combat nervous system injuries and neurodegenerative diseases. By combining high-throughput microfluidics and femtosecond laser microsurgery, we demonstrate for the first time large-scale in vivo screens for identification of compounds that affect neurite regeneration. We performed thousands of microsurgeries at single-axon precision in the nematode Caenorhabditis elegans at a rate of 20 seconds per animal. Following surgeries, we exposed the animals to a hand-curated library of approximately one hundred small molecules and identified chemicals that significantly alter neurite regeneration. In particular, we found that the PKC kinase inhibitor staurosporine strongly modulates regeneration in a concentration- and neuronal type-specific manner. Two structurally unrelated PKC inhibitors produce similar effects. We further show that regeneration is significantly enhanced by the PKC activator prostratin. National Institutes of Health (U.S.) (Director's New Innovator Award Program) (1-DP2-OD002989) David & Lucile Packard Foundation. Award in Science and Engineering Alfred P. Sloan Foundation (Award in Neuroscience) National Science Foundation (U.S.). Graduate Research Fellowship Program Merck Graduate Fellowship 2012-09-25T17:35:38Z 2012-09-25T17:35:38Z 2010-10 2010-08 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/73171 Samara, C. et al. “Large-scale in Vivo Femtosecond Laser Neurosurgery Screen Reveals Small-molecule Enhancer of Regeneration.” Proceedings of the National Academy of Sciences 107.43 (2010): 18342–18347. © 2010 National Academy of Sciences. https://orcid.org/0000-0002-4612-1962 en_US http://dx.doi.org/ 10.1073/pnas.1005372107 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences PNAS |
| spellingShingle | Gilleland, Cody Lee Rohde, Christopher Benjamin Samara, Chrysanthi Yanik, Mehmet Fatih Haggarty, Stephen J. Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration |
| title | Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration |
| title_full | Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration |
| title_fullStr | Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration |
| title_full_unstemmed | Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration |
| title_short | Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration |
| title_sort | large scale in vivo femtosecond laser neurosurgery screen reveals small molecule enhancer of regeneration |
| url | http://hdl.handle.net/1721.1/73171 https://orcid.org/0000-0002-4612-1962 |
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