Assessing Seizure Susceptibility Following Early-Life Seizures in Zebrafish

Date of Award

7-2022

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Jocelyn Lippman-Bell, PhD

Second Advisor

Denah Appelt, PhD

Third Advisor

Heather L. Montie, PPhD

Abstract

Early-life seizures (ELS) can lead to the development of epilepsy and deficits in learning and memory (Elger et al., 2004). We used the larval zebrafish pentylenetetrazole (PTZ) seizure model (Baraban et al., 2005) to investigate whether ELS lead to increased seizure susceptibility later in life. ELS were induced in zebrafish using 5 mM PTZ daily from 5-7 dpf (days post-fertilization) for 40 minutes. We hypothesized that seizure susceptibility would increase compared to controls two and three weeks after initial ELS. Thus, at 21 and 28-29 dpf, we challenged fish with a second dose of PTZ (1, 2.5, or 5 mM). We compared the response of ELS PTZ-exposed (PE) fish to that of handled (HC) and unhandled controls (UC) that did not experience ELS. Outcome measures included latency to first and second seizures, number of seizures, velocity, and time spent in fast movement. We also used immunohistochemistry (IHC) to assess synaptic changes and TUNEL to detect apoptosis. At 21 dpf, outcome measures appeared similar across groups for all outcome measures. At 28-29 dpf, UC fish had significantly more seizures than HC and PE fish at 5 mM. HC fish also had significantly higher latencies to the first and second seizures compared to UC fish at 2.5 mM. UC fish spent significantly more time in fast movement compared to HC fish at 21 dpf, while 28-29 dpf HC fish swam significantly faster than UC fish and spent significantly more time in fast movement compared to UC and PE fish. IHC pilot data suggested that ELS increased excitatory synapses in the pallium region of the telencephalon. Finally, TUNEL assay showed no signs of apoptosis in the brain from ELS. Our results did not support our hypothesis as UC and HC fish often showed significant measures of being susceptible to seizures, despite no previous PTZ exposure. This suggests a possible neuroprotective effect from ELS in zebrafish, an aspect which requires further research to help understand the mechanisms of epileptogenesis and ELS.

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