title: Model for studying Clostridium botulinum neurotoxin using differentiated motor neuron-like NG108-15 cells.
abstract: Cancerous cell lines have traditionally shown low sensitivity to laboratory or pharmaceutical preparations of botulinum neurotoxin. The work presented here demonstrates that the mouse neuroblastoma/rat glioma hybrid cell line NG108-15 is capable of more sensitively detecting BoNT/A1 than any cell line previously described. This cell line has previously been described to have motor neuron like characteristics, therefore making it a good model to study BoNTs. Differentiation of NG108-15 cells in serum-free medium containing retinoic acid and purmorphamine dramatically increased sensitivity of the neurons to BoNT/A (EC(50) = ~16 LD(50) U). Additional pre-treatment with triasialoganglioside GT1B prior to toxin exposure reduced the EC(50) further to ~11 LD(50) U. Co-culture of the neurons with C2C12 myotubes also significantly increased BoNT/A sensitivity of NG108-15 cells (EC(50) = 26 U) in the absence of differentiation factors.
authors.affiliation: Department of Bacteriology, University of Wisconsin, Madison, Madison, WI 53706, USA.
authors.forename: Regina C M
authors.initials: RC
authors.lastname: Whitemarsh
authors.forename: Christina L
authors.initials: CL
authors.lastname: Pier
authors.forename: William H
authors.initials: WH
authors.lastname: Tepp
authors.forename: Sabine
authors.initials: S
authors.lastname: Pellett
authors.forename: Eric A
authors.initials: EA
authors.lastname: Johnson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D059329:Cholinergic Neurons / Q000187:drug effects*; D003014:Clostridium botulinum; D018920:Coculture Techniques; D005732:Gangliosides / Q000494:pharmacology; D051379:Mice; D008959:Models, Neurological; D009025:Morpholines / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D051381:Rats; D014212:Tretinoin / Q000494:pharmacology
chemical_list: D005732:Gangliosides; D009025:Morpholines; D009498:Neurotoxins; D011687:Purines; D014212:Tretinoin; C016481:trisialoganglioside GT1; D019274:Botulinum Toxins, Type A; C545476:incobotulinumtoxinA; C470893:purmorphamine