title: Rapamycin suppresses PTZ-induced seizures at different developmental stages of zebrafish.
abstract: The mTORC1 complex integrates different inputs from intracellular and extracellular signals to control various cellular processes. Therefore, any disruption in the mTORC1 pathway could promote different neurological disorders. mTORC1 overactivation has been verified in different genetic and acquired epilepsy animal models. Therefore, inhibitors of this complex could have both antiepileptogenic and antiseizure effects. In our study, we investigated the effects of rapamycin pretreatment on pentylenetetrazole (PTZ)-induced seizures in zebrafish. Our results have shown that the latency to reach the tonic-clonic stage (stage III) of progressive behavioral alterations shown during PTZ-induced seizures was prolonged in larval (7days post fertilization, 7dpf), juvenile (45days post fertilization, 45dpf) and adult (6-8months) zebrafish after pretreatment with rapamycin. Furthermore, rapamycin pretreatment did not alter the locomotor activity in zebrafish. Therefore, the results obtained in our study indicate that rapamycin pretreatment is an important mechanism to control the progress of seizures in zebrafish throughout different developmental stages (larval, juvenile, and adult). Taken as a whole, our data support that rapamycin has immediate antiseizure effects and could be a potential alternative therapy for seizure control in epilepsy.
authors.affiliation: Programa de Pós-Graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Avenida Senador Attílio Fontana, 591E, 89809-000 Chapecó, SC, Brazil.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Siebel
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Prédio 12D, Sala 301, Porto Alegre, RS 90619-900, Brazil.
authors.forename: Fabiano Peres
authors.initials: FP
authors.lastname: Menezes
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Prédio 12D, Sala 301, Porto Alegre, RS 90619-900, Brazil.
authors.forename: Isabel
authors.initials: I
authors.lastname: da Costa Schaefer
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Prédio 12D, Sala 301, Porto Alegre, RS 90619-900, Brazil.
authors.forename: Bárbara Dutra
authors.initials: BD
authors.lastname: Petersen
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, Prédio 12D, Sala 301, Porto Alegre, RS 90619-900, Brazil. Electronic address: cbonan@pucrs.br.
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003292:Convulsants / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004195:Disease Models, Animal; D007814:Larva / Q000187:drug effects; D000076222:Mechanistic Target of Rapamycin Complex 1; D009043:Motor Activity / Q000187:drug effects; D046912:Multiprotein Complexes / Q000378:metabolism; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015027:Zebrafish / Q000254:growth & development / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D046912:Multiprotein Complexes; D029961:Zebrafish Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus; D010433:Pentylenetetrazole
keywords: Pentylenetetrazole; Rapamycin; Seizures; Zebrafish; mTOR