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dc.contributor.advisorNiyogi, Som
dc.contributor.advisorChivers, Doug
dc.creatorNaderi, Mohammad 1986-
dc.date.accessioned2018-10-31T14:16:07Z
dc.date.available2021-10-31T06:05:08Z
dc.date.created2018-10
dc.date.issued2018-10-31
dc.date.submittedOctober 2018
dc.identifier.urihttp://hdl.handle.net/10388/11476
dc.description.abstractI investigated the direct and transgenerational effects of chronic dietary exposure to selenium (Se) on learning and memory in zebrafish (Danio rerio), with a particular focus on alterations in dopaminergic neurotransmission. Zebrafish possess a conserved dopaminergic system with receptors homologous to mammals. However, the role of dopamine (DA) receptors in learning and memory in zebrafish was not clear. Therefore, my first two studies were focused on the role of DA receptors in learning and memory in zebrafish. To gain insights into the role of DA receptors in learning and memory in zebrafish, two different learning paradigms were employed: a latent learning task (unreinforced learning) and an associative learning task (reward-related learning). Pharmacological manipulations of DA receptors in the zebrafish brain showed that D2 receptors play a prominent role in the acquisition and consolidation of latent learning in zebrafish. While exposure to a D2 receptor family agonist impaired the acquisition and consolidation of latent learning, antagonism of D2 receptors improved both phases of latent learning in zebrafish. In the associative learning task, however, D1 receptors showed a more important role in the regulation of acquisition and consolidation of learning. In this study, exposure to both D1 receptor agonist and antagonist improved acquisition and consolidation of associative learning performance in adult zebrafish. However, manipulation of D2 receptors mainly affected retrieval of associative learning. After determining the role of DA receptors in two different forms of learning, the effects of chronic dietary exposure to Se (as selenomethionine; SeMet) on latent learning and associative learning performance in adult zebrafish were investigated in the third and fourth chapter of this thesis, respectively. Dietary exposure to high concentrations of Se (32.5 and 57.5 μg Se/g dry weight) impaired latent learning performance in zebrafish. The impaired learning was associated with the induction of oxidative stress and alterations in the mRNA expression of genes involved in DA synthesis and re-uptake in the zebrafish brain. The results of this study showed that dietary Se exposure decreased the mRNA abundance of the D1 receptor, while it increased the mRNA expression of D2 receptor subtypes in the zebrafish brain. In addition, the exposure to high concentrations of dietary Se (27.4 and 63.4 µg Se/g dry weight) also impaired associative learning performance in adult zebrafish. Similar to observations in the third chapter, Se exposure induced oxidative stress in the zebrafish brain. Moreover, an increase in DA levels of the brain was recorded, which was in line with the up-regulation of genes involved in the DA synthesis and re-uptake. However, unlike the previous study, Se exposure led to up-regulation of both D1 and D2 receptors. Following this experiment, SeMet treated female fish were bred with untreated male fish to generate the F1-generation required to investigate the transgenerational effects of dietary Se on learning and memory in zebrafish. To this end, embryos were raised up to the age of six months in clean water and fed on a normal diet, and learning performance of fish was tested in the latent learning task. Maternal exposure to dietary Se was found to impair latent learning in zebrafish offspring as well. This behavioural impairment was associated with an elevated level of DA in zebrafish brain along with an increase in the mRNA expression of genes involved in the synthesis, storage, re-uptake, and degradation of DA. In addition, the mRNA abundance of different DA receptors also showed a significant increase in the zebrafish brain. This hyperfunction of the dopaminergic system resulted in the induction of oxidative stress in the zebrafish brain. Collectively, the results of my research suggest that DA neurotransmission plays a fundamental role in learning and memory in zebrafish. However, this neurotransmitter system is highly sensitive to oxidative insult. Overall, the research presented in this thesis suggests that both chronic and maternal exposure to dietary Se leads to learning impairment in zebrafish via induction of oxidative stress and dysfunction of the dopaminergic system.
dc.format.mimetypeapplication/pdf
dc.subjectSelenium
dc.subjectLearning and Memory
dc.subjectDopamine
dc.subjectOxidative stress
dc.subjectZebrafish
dc.titleEffects of chronic exposure to selenium on learning and memory in zebrafish (Danio rerio)
dc.typeThesis
dc.date.updated2018-10-31T14:16:07Z
thesis.degree.departmentBiology
thesis.degree.disciplineBiology
thesis.degree.grantorUniversity of Saskatchewan
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)
dc.type.materialtext
dc.contributor.committeeMemberFerrari, Maud
dc.contributor.committeeMemberJanz, David
dc.contributor.committeeMemberMorrissey , Christy
dc.contributor.committeeMemberWilson, Ken
local.embargo.terms2021-10-31


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