Type C botulinum toxin causes degeneration of motoneurons in vivo.
All botulinum toxins (BoNTs, types A-G) inhibit synaptic transmitter release from motoneurons, and thus result in respiratory arrest and death. Rapid treatment with anti-BoNT antibodies can prevent progression, but recovery still requires weeks on a ventilator. Even after recovery, there is a potential for persistent fatigue in some cases of botulism even years after the insult, possibly because of motoneuron dropout for previously unknown reasons. Unique among BoNTs, the C-type (BoNT/C) cleaves two proteins involved in neurotransmitter release, syntaxin and SNAP-25, and induces apoptotic cell death in cultured cerebellar neurons. It is not clear, however, whether BoNT/C also affects neurons that encounter toxin in vivo, namely motoneurons. Here, we provide experimental evidence that BoNT/C causes a slow degeneration of motoneurons both in vitro and in vivo. This novel form of BoNT/C-induced cell death may require new treatment strategies.
Zhao
Li-Chun
LC
Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California, USA.|School of Pharmacy, Jilin University, Changchun, China.
Yang
Bo
B
Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California, USA.
Wang
Rengang
R
Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California, USA.
Lipton
Stuart A
SA
Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California, USA.
Zhang
Dongxian
D
Center for Neuroscience, Aging and Stem Cell Research, Burnham Institute for Medical Research, La Jolla, California, USA.
D000818:Animals; D001905:Botulinum Toxins / Q000633:toxicity*; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D007839:Functional Laterality; D054501:Group II Phospholipases A2; D007211:Indoles; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000187:drug effects*; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D011042:Poisons / Q000633:toxicity*; D013116:Spinal Cord / Q000166:cytology
D007211:Indoles; D016900:Neurofilament Proteins; D011042:Poisons; C051774:neurofilament protein H; C007293:DAPI; D054501:Group II Phospholipases A2; D001905:Botulinum Toxins; C096324:botulinum toxin type C