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Updated: Apr 11, 2026
Behavioral And Physiological Analysis In A Zebrafish Model Of Epilepsy
Published on: October 19, 2021
Rapamycin suppresses PTZ-induced seizures at different developmental stages of zebrafish
Anna Maria Siebel1, Fabiano Peres Menezes2, Isabel da Costa Schaefer2
1Programa de Pós-Graduação em Ciências Ambientais, Universidade Comunitária da Região de Chapecó, Avenida Senador Attílio Fontana, 591E, 89809-000 Chapecó, SC, Brazil.
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.
Insights
Rapamycin pretreatment prolonged seizure latency in zebrafish across all developmental stages. This mTORC1 inhibitor demonstrated antiseizure effects without impacting locomotor activity, suggesting potential epilepsy therapy.
Area of Science:
- Neuroscience
- Pharmacology
- Developmental Biology
Background:
- The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cellular processes and its disruption is linked to neurological disorders.
- mTORC1 overactivation is observed in epilepsy models, suggesting inhibitors could offer therapeutic benefits.
- Pentylenetetrazole (PTZ) is a common agent used to induce seizures in animal models for epilepsy research.
Purpose of the Study:
- To investigate the antiepileptogenic and antiseizure effects of rapamycin, an mTORC1 inhibitor.
- To evaluate the impact of rapamycin pretreatment on pentylenetetrazole (PTZ)-induced seizures in zebrafish at different life stages.
Main Methods:
- Zebrafish (larval, juvenile, and adult) were pretreated with rapamycin.
- PTZ was administered to induce seizures, and the latency to reach the tonic-clonic stage (stage III) was recorded.
- Locomotor activity was monitored to assess potential side effects of rapamycin.
Main Results:
- Rapamycin pretreatment significantly prolonged the seizure latency in PTZ-treated zebrafish across larval, juvenile, and adult stages.
- The antiseizure effect of rapamycin was observed throughout different developmental phases.
- Rapamycin pretreatment did not adversely affect the baseline locomotor activity of the zebrafish.
Conclusions:
- Rapamycin exhibits immediate antiseizure effects, demonstrating its potential as an antiepileptogenic agent.
- The findings support rapamycin as a potential therapeutic strategy for controlling seizures in epilepsy.
- Rapamycin's efficacy across developmental stages highlights its broad applicability in seizure management.
