title: BoNT/E prevents seizure-induced activation of caspase 3 in the rat hippocampus.
abstract: Clinical and experimental studies clearly demonstrate that prolonged seizures and status epilepticus induce neuronal cell death in the brain. Recent evidence suggests that induction of apoptosis contributes greatly to seizure-induced brain damage. We recently demonstrated that intrahippocampal delivery of botulinum neurotoxin E (BoNT/E) in the rat hippocampus is able to prevent neuronal loss, which occurs after kainic-acid-induced seizures. Here, we investigated the molecular mechanisms of BoNT/E-mediated neuroprotection. We found that intrahippocampal administration of BoNT/E prevents the upregulation of apoptotic proteins (phosphorylated c-Jun and cleaved caspase 3), which occurs in hippocampal neurones following kainic acid seizures. These results demonstrate that the neuroprotective action of BoNT/E on seizure-injured hippocampal neurons involves the blockade of well-characterized apoptotic pathways.
authors.affiliation: Istituto di Neuroscienze del CNR, via Moruzzi 1, 56100 Pisa, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Manno
authors.forename: Flavia
authors.initials: F
authors.lastname: Antonucci
authors.forename: Matteo
authors.initials: M
authors.lastname: Caleo
authors.forename: Yuri
authors.initials: Y
authors.lastname: Bozzi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001905:Botulinum Toxins / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D007608:Kainic Acid; D008297:Male; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; C505410:Casp3 protein, rat; D053148:Caspase 3; D001905:Botulinum Toxins; D007608:Kainic Acid; C096326:botulinum toxin type E