PUBLICATION
Rapamycin suppresses PTZ-induced seizures at different developmental stages of zebrafish
- Authors
- Siebel, A.M., Menezes, F.P., da Costa Schaefer, I., Petersen, B.D., Bonan, C.D.
- ID
- ZDB-PUB-150609-14
- Date
- 2015
- Source
- Pharmacology, biochemistry, and behavior 139 Pt B: 163-8 (Journal)
- Registered Authors
- Bonan, Carla Denise
- Keywords
- mTOR, pentylenetetrazol, rapamycin, seizures, zebrafish
- MeSH Terms
-
- Animals
- Anticonvulsants/pharmacology*
- Convulsants/antagonists & inhibitors*
- Convulsants/toxicity*
- Disease Models, Animal
- Larva/drug effects
- Motor Activity/drug effects
- Multiprotein Complexes/metabolism
- Pentylenetetrazole/antagonists & inhibitors*
- Pentylenetetrazole/toxicity*
- Seizures/chemically induced
- Seizures/prevention & control*
- Signal Transduction/drug effects
- Sirolimus/pharmacology*
- TOR Serine-Threonine Kinases/metabolism
- Zebrafish/growth & development
- Zebrafish/physiology*
- Zebrafish Proteins/metabolism
- PubMed
- 26051026 Full text @ Pharmacol. Biochem. Behav.
Citation
Siebel, A.M., Menezes, F.P., da Costa Schaefer, I., Petersen, B.D., Bonan, C.D. (2015) Rapamycin suppresses PTZ-induced seizures at different developmental stages of zebrafish. Pharmacology, biochemistry, and behavior. 139 Pt B:163-8.
Abstract
The mTORC1 complex integrates different inputs from intracellular and extracellular signals to the control of various cellular processes. Therefore, any disruption in 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 pentylenetetrazol (PTZ)-induced seizures in zebrafish. Our results have shown that the latency to reach the tonic-clonic stage (stage III) of progressive behavior alterations showed during PTZ-induced seizures was prolonged in larvae (7days post fertilization, 7 dpf), juvenile (45days 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping