Rapamycin suppresses PTZ-induced seizures at different developmental stages of zebrafish

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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 (7 days post fertilization, 7 dpf), juvenile (45 days post fertilization, 45 dpf) and adult (6–8 months) 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.

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