Screening a Small Organic Compound for Potential Antiseizure Activity in the Zebrafish PTZ Model

Undergraduate #230
Board Location: #113
Discipline: Neuroscience
Session: 1

Hope-Abigail Mbanga - University of Maryland Eastern Shore
Co-Author(s): Rhashanda Haywood; Patrice Jackson-Ayotunde, Ph.D; Tracy Bell, Ph.D.



Epilepsy, a chronic neurological disorder, affects over 70 million people globally. Despite the availability of more than twenty antiseizure drugs for the symptomatic treatment of epileptic seizures, approximately one-third of patients suffer from drug-resistant epilepsy. T-type calcium channels play a critical role in epilepsy, making them an important target for therapeutic intervention. This study evaluated the effects of the novel compound RHB62, known for its activity against T-type calcium channels, in a zebrafish model of pentylenetetrazole (PTZ)-induced seizures. Adult zebrafish were weighed and anesthetized in an ice water bath, followed by a single intraperitoneal (i.p.) injection of either 1% DMSO or 50 mg/kg RHB62 dissolved in 1% DMSO. After a 15-minute recovery, the fish were injected with PTZ (170 mg/kg, i.p.). Behavioral activity was manually observed and video-tracked using EthoVision software for fifteen minutes. Brain tissue was dissected and processed for qPCR analysis to evaluate the expression of early immediate genes linked to epilepsy. Although no significant difference was found in the expression of these genes, RHB62 reduced PTZ-induced swimming behaviors and locomotor activity, lessening the severity of seizure-like behaviors. These results indicate that RHB62 has antiseizure effects in the PTZ zebrafish model. Further research is needed to understand how RHB62 modulates seizure activity and to assess its potential as a treatment for drug resistant epilepsy.

Funder Acknowledgement(s): National Science Foundation under Grant #HRD 1619676

Faculty Advisor: Dr. Tracy Bell, tdbell@umes.edu

Role: Assisted in studying the effects of RHB62 on seizure-like behaviors in a PTZ-induced zebrafish model. Responsibilities included administering compound and PTZ to zebrafish via injection, observing and recording zebrafish swimming behaviors to identify changes related to seizure activity, dissecting zebrafish brain, conducting PCR tests to determine gene expression, and analyzing results.