The Behavioural, Neuroanatomical, and Molecular Effects of Chronic Social Stress on Mice That Lack Zinc Transporter 3 and Vesicular Zinc

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dc.contributor.advisorDyck, Richard H.
dc.contributor.authorMcAllister, Brendan Barrymore
dc.contributor.committeememberAntle, Michael C.
dc.contributor.committeememberTrang, Tuan
dc.contributor.committeememberPittman, Quentin J.
dc.contributor.committeememberTzounopoulos, Thanos
dc.date2019-06
dc.date.accessioned2018-12-06T17:40:54Z
dc.date.available2018-12-06T17:40:54Z
dc.date.issued2018-12-04
dc.description.abstractIn certain neurons, zinc ions are stored in synaptic vesicles by a dedicated vesicular zinc transporter, called zinc transporter 3 (ZnT3). Vesicular zinc can then be released synaptically, in an activity-dependent fashion, to transmit signals by modulating a plethora of targets. To understand the function of vesicular zinc in the central nervous system, a useful tool is the ZnT3 knockout (KO) mouse, which lacks ZnT3 and, as a result, lacks vesicular zinc. Behavioural characterization of these mice has revealed subtle abnormalities in cognition and sensory processing. In addition, a pattern is becoming apparent, wherein ZnT3 KO mice behave normally under standard laboratory conditions but fail to exhibit neural plasticity and behavioural adaptation in response to certain treatments or experiences. The experiments described in this thesis were designed to assess how ZnT3 KO mice would respond to the experience of repeated social defeat (RSD) stress, a method of modelling depression-like behaviour in rodents, and to test the hypothesis that ZnT3 KO mice would fail to exhibit stress-induced neural plasticity, resulting in an altered behavioural response to stress. The primary finding was that, compared to wild type (WT) mice, ZnT3 KO mice exhibited reduced social avoidance of a novel conspecific following RSD, suggesting reduced susceptibility to the depression-like behaviour of social withdrawal. Both genotypes were equally susceptible to anxiety-like behaviour following RSD, however. To investigate the mechanisms behind the seemingly protective effect of eliminating vesicular zinc on stress-induced social avoidance, several neuroanatomical parameters were examined. No evidence was found that microglial activation, hippocampal neurogenesis, or hippocampal brain-derived neurotrophic factor (BDNF) levels could account for the difference in behavioural outcome. However, some evidence was found that altered structure of the corpus callosum or reduced BDNF levels in the nucleus accumbens may contribute to the protection against social avoidance in ZnT3 KO mice. Further work will be required to validate and extend these findings, in order to more fully understand the mechanisms behind the altered behavioural response to chronic stress – and the altered capacity for experience-dependent neuroplasticity – in mice that lack vesicular zinc.en_US
dc.identifier.citationMcAllister, B. B. (2018). The behavioural, neuroanatomical, and molecular effects of chronic social stress on mice that lack zinc transporter 3 and vesicular zinc (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/34901en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/34901
dc.identifier.urihttp://hdl.handle.net/1880/109238
dc.language.isoeng
dc.publisher.facultyArts
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectZinc
dc.subjectZnT3
dc.subjectStress
dc.subjectNeurogenesis
dc.subjectFluoxetine
dc.subjectBDNF
dc.subject.classificationNeuroscienceen_US
dc.titleThe Behavioural, Neuroanatomical, and Molecular Effects of Chronic Social Stress on Mice That Lack Zinc Transporter 3 and Vesicular Zinc
dc.typedoctoral thesis
thesis.degree.disciplinePsychology
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
ucalgary.item.requestcopytrue
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