Development of a scn1a Null Zebrafish Model for Screening Potential Anti-Epileptic Natural Products

Lipson, Patricia Ann (2018) Development of a scn1a Null Zebrafish Model for Screening Potential Anti-Epileptic Natural Products. Undergraduate thesis, under the direction of Dr. Kristine Willett from BioMolecular Sciences, The University of Mississippi.

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Epilepsy affects around 50 million people in the world. Thus, it is imperative that new more effective and safe treatments be found. This study was designed to use zebrafish to screen potential anti-epileptic natural products. We utilized two scn1Lab null zebrafish models (morpholino-injected fish where scn1Lab was transiently knocked down and a transgenic scn1Lab -/- fish line). Alternatively, we used AB wildtype fish to test compounds in a chemically-induced seizure model. Natural compounds including cannabidiol, CBD, and Tapinanthus globiferous, TG, extracts were screened for their anti-seizure activity. When scn1Lab -/- fish were treated with CBD (0.075 and 0.3 mg/L) from 5 to 7 days post fertilization (dpf), a non-significant reduction of seizure-like activity, compared to control, was found. Additional exposures are needed to verify this reduction. In wildtype fish where seizures were induced by treatment of pentylenetetrazole, TG extracts were tested for anti-epileptic potential from 5 to 6 dpf. Our results showed that one extract of TG, AF.1.11.TG.4 (0.2, 1, and 5 mg/L) showed some promise in reducing seizure-like activity. We conclude that certain extracts of TG show promise as anticonvulsants, and CBD requires further research to verify its reduction. The transgenic scn1Lab -/- fish once acquired and raised proved to a better model for screening natural products for Dravet-specific seizures than morpholino-based approaches.

Item Type: Thesis (Undergraduate)
Creators: Lipson, Patricia Ann
Student's Degree Program(s): Biochemistry
Thesis Advisor: Dr. Kristine Willett
Thesis Advisor's Department: BioMolecular Sciences
Institution: The University of Mississippi
Subjects: R Medicine > RM Therapeutics. Pharmacology
Depositing User: Patricia Lipson
Date Deposited: 17 May 2018 21:37
Last Modified: 17 May 2018 21:37

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