Please use this identifier to cite or link to this item:
http://hdl.handle.net/11375/23747
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Murphy, Kathryn | - |
dc.contributor.author | Mancini, Steven | - |
dc.date.accessioned | 2019-01-16T15:28:08Z | - |
dc.date.available | 2019-01-16T15:28:08Z | - |
dc.date.issued | 2018 | - |
dc.identifier.uri | http://hdl.handle.net/11375/23747 | - |
dc.description.abstract | Developing brains have a great capacity for plasticity, whereas plasticity in adulthood is much more limited. However, the mature brain still retains a considerable amount of plasticity that can be augmented by a variety of plasticity-enhancing therapeutics. Two approaches include the antidepressant fluoxetine and environmental enrichment. Both induce functional improvements in multiple brain regions and produce alterations in both inhibitory as well as excitatory synaptic mechanisms. Multiple gene expression changes induced by fluoxetine and enrichment have been demonstrated including the alteration of mRNAs and proteins implicated in synaptic plasticity, dendritic spine morphology, cell signalling, survival, metabolism, molecular transport, transcription, histone deacetylation, and protein degradation. However, how these treatments work at the molecular level to bring about enhanced plasticity in adulthood is still not completely understood. We investigated the effects of fluoxetine, alone or in combination with monocular deprivation (MD), in the adult rat visual cortex and examined the impact of short- and long-term enrichment in the adult rat somatomotor cortex. We studied a collection of synaptic and non-neuronal proteins implicated in experience-dependent plasticity, including excitatory markers (PSD-95, GluN1); spine markers (Drebrin A - mature isoform, Drebrin E - immature isoform, Ube3A); and a myelin marker (Classic MBP). Protein expression was quantified using Western blot analysis. Enrichment produced modest changes in PSD-95 and GluN1 levels, with short- iv term enrichment favouring a decrease in both excitatory markers. Interestingly, fluoxetine and enrichment elicited distinct effects on dendritic spine markers. Fluoxetine resulted in an overall reduction of dendritic spine markers, whereas enrichment shifted Drebrin levels to favour more Drebrin A relative to Drebrin E. Additionally, fluoxetine appeared to substantially rescue Ube3A losses that resulted from MD while enrichment exerted modest effects on Ube3A levels. We also found that MD increased MBP in the ipsilateral hemisphere but decreased MBP in the contralateral hemisphere, changes that were independent of fluoxetine. MBP was also elevated with enrichment. These findings suggest that changes in MBP are predominantly driven by changes in experience. This research identifies several plasticity mechanisms, including alterations in dendritic spine dynamics, effects on Ube3A-related plasticity, and experience-dependent MBP fluctuations, that fluoxetine and enrichment use to enhance adult brain plasticity and reactivate heightened plasticity in adulthood. | en_US |
dc.language.iso | en | en_US |
dc.title | ENHANCING PLASTICITY WITH FLUOXETINE AND ENRICHMENT IN THE ADULT RAT CORTEX | en_US |
dc.type | Thesis | en_US |
dc.contributor.department | Neuroscience | en_US |
dc.description.degreetype | Thesis | en_US |
dc.description.degree | Master of Science (MSc) | en_US |
dc.description.layabstract | The brain’s ability to change in response to new experiences, called neuroplasticity, is high during development and declines into adulthood. Remarkably, the adult brain still retains a considerable amount of plasticity, but generally requires some assistance in order to activate it. My thesis investigates two treatments that aim to boost adult brain plasticity and reinstate the increased flexibility of young brains in adulthood. The first treatment is the drug fluoxetine. The second treatment is environmental enrichment. In my thesis, I measure the expression levels of several proteins to study how these treatments enhance plasticity in adulthood. I found that fluoxetine and enrichment exert distinct effects on dendritic spines, which are small protrusions on neurons that play a key role in processing and transmitting information. My findings also indicate that myelin, a physical structure that has generally been thought to prevent plastic changes, may actually help support plasticity. | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Mancini_Steven_J_2018August_MSc.pdf | 6.71 MB | Adobe PDF | View/Open |
Items in MacSphere are protected by copyright, with all rights reserved, unless otherwise indicated.