Forebrain glutamate uptake and behavioral parameters are altered in adult zebrafish after the induction of Status Epilepticus by kainic acid

Neurotoxicology. 2018 Jul:67:305-312. doi: 10.1016/j.neuro.2018.04.007. Epub 2018 Apr 19.

Abstract

The development of new antiepileptic drugs is a high-risk/high-cost research field, which is made even riskier if the behavioral epileptic seizure profile is the unique approach on which the development is based. In order to increase the effectiveness of the screening conducted in the zebrafish model of status epilepticus (SE), the evaluation of neurochemical markers of SE would be of great relevance. Epilepsy is associated with changes in the glutamatergic system, and glutamate uptake is one of the critical parameters of this process. Therefore, we evaluated the levels of glutamate uptake in the zebrafish brain and analyzed its correlation with the progression of behavioral changes in zebrafish at different times after the administration of kainic acid (5 mg/kg). The results showed that the zebrafish suffered with lethargy while swimming for up to 72 h after SE, had reduced levels of GFAP cells 12 h after SE, reduced levels of S100B up to 72 h after SE, and reduced levels of glutamate uptake in the forebrain between 3 h and 12 h after SE. The forebrain region of adult zebrafish after SE present similar changes to the neurochemical limbic alterations that are seen in rodent models of SE. This study demonstrated that there is a time window in which to use the KA zebrafish model of SE to explore some of the known neurochemical alterations that have been observed in rodent models of epilepsy and epileptic human patients.

Keywords: Behavior; GFAP; Glutamate uptake; Kainic acid; S100B; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Glutamic Acid / metabolism*
  • Kainic Acid / toxicity*
  • Locomotion / drug effects*
  • Locomotion / physiology
  • Male
  • Prosencephalon / drug effects
  • Prosencephalon / metabolism*
  • Status Epilepticus / chemically induced*
  • Status Epilepticus / metabolism*
  • Zebrafish

Substances

  • Glutamic Acid
  • Kainic Acid