Toxicity of botulinum neurotoxins in central nervous system of mice.
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 x 10(-6)mg/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 regained the initial healthy conditions. At sub-lethal doses, the same clinical signs appear in a lighter form and with a longer time course.
Luvisetto
Siro
S
Istituto di Neuroscienze del CNR, Sez. di Psicobiologia e Psicofarmacologia, V.le Marx 15/43, 00137 Roma, Italy. s.luvisetto@ipsifar@rm.cnr.it
Rossetto
Ornella
O
Montecucco
Cesare
C
Pavone
Flaminia
F
D000818:Animals; D001763:Blepharoptosis / Q000139:chemically induced; D001905:Botulinum Toxins / Q000008:administration & dosage / Q000633:toxicity*; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000633:toxicity*; D002490:Central Nervous System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005094:Exophthalmos / Q000139:chemically induced; D007276:Injections, Intraventricular; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010863:Piloerection / Q000187:drug effects; D013997:Time Factors; D015431:Weight Loss / Q000187:drug effects
C096323:rimabotulinumtoxinB; D001905:Botulinum Toxins; D019274:Botulinum Toxins, Type A