Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration
Author(s)
Gilleland, Cody Lee; Rohde, Christopher Benjamin; Samara, Chrysanthi; Yanik, Mehmet Fatih; Haggarty, Stephen J.
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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.
Date issued
2010-10Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer ScienceJournal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
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.
Version: Final published version
ISSN
0027-8424
1091-6490