eprintid: 34971
rev_number: 17
eprint_status: archive
userid: 8205
dir: disk0/00/03/49/71
datestamp: 2024-06-14 08:19:30
lastmod: 2024-06-18 12:52:54
status_changed: 2024-06-14 08:19:30
type: doctoralThesis
metadata_visibility: show
creators_name: Fischer, Sabeth Maria Sheela
title: Impact of neurotoxic substances on the development and behavior of zebrafish embryos
Case studies with nicotine, desnitro-imidacloprid
and three antidepressants
subjects: ddc-570
divisions: i-140001
adv_faculty: af-14
cterms_swd: zebrafish embryo
cterms_swd: behavior
cterms_swd: FET
abstract: The zebrafish embryo as an alternative complex vertebrate model can be utilized as a valuable tool for assessing developmental neurotoxicity. Analysis of embryonic behavior in particular can be used to detect even subtle changes that may later have serious effects on the fitness of the organism. However, since behavior is a sensitive endpoint, it can be influenced by various confounding factors. I implemented a generalized additive modeling (GAM) approach to account for natural variability of the fish and discriminate treatment-related alterations in the tail coiling behavior from several cofounding factors. To complement this analysis, I inspected the integrity of secondary motoneurons and skeletal muscle using antibody staining and birefringence microscopy, respectively. The impairments of both structural endpoints align with the behavior outcomes. After successful proof-of-concept, I used the GAM approach to investigate a suspected metabolite of the insecticide imidacloprid, desnitro-imidacloprid. Here, I could not detect a significant alteration compared to the control. At least for zebrafish, I conclude that desnitro-imidacloprid does not show a comparable developmental neurotoxic potential like nicotine. Finally, I investigated the impacts of the antidepressants sertraline, paroxetine and venlafaxine on the zebrafish embryo. Shared effects of all three compounds in the FET test included cardiotoxicity, degeneration of the fin seam and a loss of equilibrioception. Experiments on sublethal developmental neurotoxic effects on embryonic behavior showed altered movement patterns and lower visual-motor response to a light stressor in a concentration dependent manner for all substances. I concluded that antidepressants could lower the fish embryos´ fitness by impacting heart health and equilibrium while swimming. In the case of sertraline, embryonic behavioral alterations have been visible at environmentally relevant concentrations and thus it can pose a realistic threat to fish in the aquatic environment. Behavior as an endpoint, and in particular the coiling movements, has been shown to be the most sensitive to detect potential developmental neurotoxicity.
date: 2024
id_scheme: DOI
id_number: 10.11588/heidok.00034971
ppn_swb: 1891483609
own_urn: urn:nbn:de:bsz:16-heidok-349715
date_accepted: 2024-04-26
advisor: HASH(0x561a62b891d0)
language: eng
bibsort: FISCHERSABIMPACTOFNE2024
full_text_status: public
place_of_pub: Heidelberg
citation:   Fischer, Sabeth Maria Sheela  (2024) Impact of neurotoxic substances on the development and behavior of zebrafish embryos Case studies with nicotine, desnitro-imidacloprid and three antidepressants.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/34971/1/Doktorarbeit_2024_Maria_Fischer.pdf