Toxicity during early development of the mouse nervous system of a scorpion neurotoxin active on sodium channels.
The lethal effects of scorpion envenomation is due to neurotoxins active on voltage-sensitive sodium channels. Dysfunctions of the peripheral and central nervous systems with neurological manifestations are commonly observed after scorpion stings, specially in young children. Since the neurotoxicity of venom fraction is greatly higher by intracerebroventricular than by subcutaneous injections, a direct effect of venom on CNS cannot be excluded specially in infants where the blood-brain barrier is not fully functional. We investigated the activity of a neurotoxin from the scorpion Androctonus australis hector (AahII) in newborn mice at 3, 7 and 14 days after birth and in adults. Young mice (P3, P7) were more sensitive to AahII injected subcutaneously than were adults, but were less sensitive to intracerebroventricular injection. The affinity of AahII for its receptor site on brain synaptosomes from P3 and P7 mice was slightly higher and the density of the binding sites was half that of adult mice. After subcutaneous injection of [125I]-AahII it was also observed that a small amount of radioactivity was found in brains of neonate mice but not in that of adults. This amount is however extremely lower than the value of the LD50 determined by intracerebroventricular injection. Results are consistent with a peripheral action of AahII and show that its toxic activity changes during the mouse nervous system development.
Clot-Faybesse
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Ingénierie des Protéines, CNRS UMR 6560, IFR Jean Roche, Faculté de Médecine-Nord, Univ Mediterranee, Marseille, France.
Guieu
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Rochat
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Devaux
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D000367:Age Factors; D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D007928:Lethal Dose 50; D051379:Mice; D008810:Mice, Inbred C57BL; D009420:Nervous System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012604:Scorpion Venoms / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D015222:Sodium Channels / Q000187:drug effects*; D013574:Synaptosomes / Q000378:metabolism
D012604:Scorpion Venoms; D015222:Sodium Channels