Toxicity of botulinum neurotoxins in central nervous system of mice

Siro Luvisetto, Ornella Rossetto, Cesare Montecucco, Flaminia Pavone

Research output: Contribution to journalArticlepeer-review

Abstract

Botulinum neurotoxins (BoNTs) act specifically on cholinergic nerve terminals, where they cause a sustained block of acetylcholine release, and therefore they are powerful tools to study the role of cholinergic neurons in neuronal processes. Peripheral effects of BoNTs are widely documented while central effects have not been studied. Here, we report for the first time on the central toxicity of BoNT serotypes A and B following their direct intracerebroventricular (icv) injection in CD1 mice. The LD50 values were found to be in the range 0.5-1.0×10-6mg/kg. We recorded the following signs preceding animal death: piloerection and weight decrease appear first, followed by temperature decrease, eyelid closure, loss of sensorimotor reflexes, dehydration, dyspnea. Mice died of heart or respiratory failure. The surviving mice recovered completely within 4-6 days and reacquired the initial healthy conditions. At sub-lethal doses, the same clinical signs appear in a lighter form and with a longer time course.

Original languageEnglish
Pages (from-to)475-481
Number of pages7
JournalToxicon
Volume41
Issue number4
DOIs
Publication statusPublished - Apr 1 2003

Keywords

  • Botulinum neurotoxins
  • Central nervous system
  • Mice
  • SNARE proteins

ASJC Scopus subject areas

  • Toxicology

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