Investigation of the rapid-acting antidepressant-like effects of reelin in parallel to ketamine
| dc.contributor.author | Johnston, Jenessa | |
| dc.contributor.supervisor | Caruncho, Hector J. | |
| dc.contributor.supervisor | Kalynchuk, Lisa E. | |
| dc.date.accessioned | 2023-04-14T23:20:03Z | |
| dc.date.available | 2023-04-14T23:20:03Z | |
| dc.date.copyright | 2022 | en_US |
| dc.date.issued | 2023-04-14 | |
| dc.degree.department | Division of Medical Sciences | en_US |
| dc.degree.level | Doctor of Philosophy Ph.D. | en_US |
| dc.description.abstract | Ketamine, an N-methyl-D-aspartate antagonist, presented one of the first major breakthroughs in decades of antidepressant research. Ketamine’s clinical effects take place within hours in patients with treatment-resistant depression. It is also able to ameliorate some of the most stubborn symptoms such as anhedonia and suicidal ideation. However, the exact underlying mechanisms are still yet unknown. In addition, extrapyramidal side effects and potential health risks limit the use of ketamine to certain populations. Reelin, an extracellular matrix glycoprotein, has been demonstrated to be downregulated in the hippocampus of patients with depression. Preliminary research from our lab has demonstrated that exogenous reelin administration may have fast-acting antidepressant effects, though its signaling pathways and effects on synaptic plasticity are still unknown. However, a significant amount of research on fast-acting antidepressants has directed attention to the upregulation of excitatory signaling in areas such as the hippocampus, through various cellular signaling pathways such as mTORC1 activation. This increase in excitatory signaling, particularly through increases in AMPAR transmission, has been heavily implicated in ketamine’s antidepressant, but not dissociative, effects. With a lens to increasing the translatability of findings from bench to bedside, this dissertation first discusses the inclusion of people with lived experience in the earliest stages of research. Following this, the underlying mechanisms of reelin are researched in a variety of methods in order to provide a broad picture of reelin as a putative rapid-acting antidepressant. | en_US |
| dc.description.scholarlevel | Graduate | en_US |
| dc.identifier.bibliographicCitation | Johnston, J. N., Ridgway, L., Cary-Barnard, S., Allen, J., Sanchez-Lafuente, C. L., Reive, B., ... & Caruncho, H. J. (2021). Patient oriented research in mental health: matching laboratory to life and beyond in Canada. Research Involvement and Engagement, 7(1), 1-11. | en_US |
| dc.identifier.bibliographicCitation | Johnston, J. N., Thacker, J. S., Desjardins, C., Kulyk, B. D., Romay-Tallon, R., Kalynchuk, L. E., & Caruncho, H. J. (2020). Ketamine rescues hippocampal reelin expression and synaptic markers in the repeated-corticosterone chronic stress paradigm. Frontiers in Pharmacology, 11, 1387. | en_US |
| dc.identifier.bibliographicCitation | Brymer, K. J., Johnston, J., Botterill, J. J., Romay-Tallon, R., Mitchell, M. A., Allen, J., ... & Kalynchuk, L. E. (2020). Fast-acting antidepressant-like effects of Reelin evaluated in the repeated-corticosterone chronic stress paradigm. Neuropsychopharmacology, 45(10), 1707-1716. | en_US |
| dc.identifier.uri | http://hdl.handle.net/1828/14945 | |
| dc.language | English | eng |
| dc.language.iso | en | en_US |
| dc.rights | Available to the World Wide Web | en_US |
| dc.subject | Depression | en_US |
| dc.subject | Reelin | en_US |
| dc.subject | Ketamine | en_US |
| dc.subject | Chronic Stress | en_US |
| dc.title | Investigation of the rapid-acting antidepressant-like effects of reelin in parallel to ketamine | en_US |
| dc.type | Thesis | en_US |