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.
MetadataShow full item record
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.
DepartmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Proceedings of the National Academy of Sciences
National Academy of Sciences
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.
Final published version