Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures. Academic Article uri icon

Overview

abstract

  • The availability of animal models of epileptic seizures provides opportunities to identify novel anticonvulsants for the treatment of people with epilepsy. We found that exposure of 2-day-old zebrafish embryos to the convulsant agent pentylenetetrazole (PTZ) rapidly induces the expression of synaptic-activity-regulated genes in the CNS, and elicited vigorous episodes of calcium (Ca(2+)) flux in muscle cells as well as intense locomotor activity. We then screened a library of ∼2000 known bioactive small molecules and identified 46 compounds that suppressed PTZ-inducedtranscription of the synaptic-activity-regulated gene fos in 2-day-old (2 dpf) zebrafish embryos. Further analysis of a subset of these compounds, which included compounds with known and newly identified anticonvulsant properties, revealed that they exhibited concentration-dependent inhibition of both locomotor activity and PTZ-induced fos transcription, confirming their anticonvulsant characteristics. We conclude that this in situ hybridisation assay for fos transcription in the zebrafish embryonic CNS is a robust, high-throughput in vivo indicator of the neural response to convulsant treatment and lends itself well to chemical screening applications. Moreover, our results demonstrate that suppression of PTZ-induced fos expression provides a sensitive means of identifying compounds with anticonvulsant activities.

publication date

  • June 21, 2012

Research

keywords

  • Anticonvulsants
  • Disease Models, Animal
  • Epilepsy
  • Zebrafish

Identity

PubMed Central ID

  • PMC3484860

Scopus Document Identifier

  • 84870028642

Digital Object Identifier (DOI)

  • 10.1242/dmm.010090

PubMed ID

  • 22730455

Additional Document Info

volume

  • 5

issue

  • 6