PUBLICATION
Development and validation of chemical kindling in adult zebrafish: A simple and improved chronic model for screening of antiepileptic agents
- Authors
- Kumari, S., Sharma, P., Mazumder, A.G., Rana, A.K., Sharma, S., Singh, D.
- ID
- ZDB-PUB-200822-10
- Date
- 2020
- Source
- Journal of Neuroscience Methods 346: 108916 (Journal)
- Registered Authors
- Singh, Damanpreet
- Keywords
- Danio rerio, Epilepsy, Pentylenetetrazole, Valproic acid, c-fos, cAMP response element binding protein
- MeSH Terms
-
- Animals
- Anticonvulsants*/pharmacology
- Kindling, Neurologic*
- Pentylenetetrazole/toxicity
- Seizures/chemically induced
- Seizures/drug therapy
- Zebrafish
- PubMed
- 32818549 Full text @ J. Neurosci. Methods
Citation
Kumari, S., Sharma, P., Mazumder, A.G., Rana, A.K., Sharma, S., Singh, D. (2020) Development and validation of chemical kindling in adult zebrafish: A simple and improved chronic model for screening of antiepileptic agents. Journal of Neuroscience Methods. 346:108916.
Abstract
Background Zebrafish has emerged out to be a potential animal model of acute convulsion for early screening of antiepileptic agents. There is a need of alternative chronic zebrafish models of epilepsy with more correlation to clinical condition.
New method Adult zebrafish were repeatedly exposed to subeffective concentrations of pentylenetetrazole (PTZ), until appearance to tonic-clonic like seizures, considered as kindled. Valproic acid (VPA) exposure was given during kindling, and in kindled fish in 02 different groups. The neurotransmitters level and expression of the genes associated with kindling were studied in the fish brain.
Results There was increase in seizure severity score at 1.25 mM concentration of PTZ, and 66.66 % of fish achieved kindling after 22 days' exposure. A marked increase in the expression of c-fos, crebbpa and crebbpb, and glutamate/GABA level was observed in kindled fish. VPA inhibited induction of PTZ-mediated kindling, and reduced seizures in kindled fish.
Comparison with existing method In contrast to an existing zebrafish kindling method, the present kindling protocol is of longer duration, with more similarity to clinical epilepsy. Moreover, the induction of kindling involves a simple non-invasive technique, without use of anesthesia. The protocol can be used for evaluation of both, antiepileptic and antiepileptogenic agents.
Conclusion Repeated exposure of 1.25 mM PTZ induced kindling in zebrafish, with alteration in the brain neurotransmitter levels and gene expression. Inhibition of kindling induction, and decrease in seizures in normal and kindled fish, respectively by VPA validated application of the model for preclinical testing of agents against epilepsy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping