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http://hdl.handle.net/11375/23747
Title: | ENHANCING PLASTICITY WITH FLUOXETINE AND ENRICHMENT IN THE ADULT RAT CORTEX |
Authors: | Mancini, Steven |
Advisor: | Murphy, Kathryn |
Department: | Neuroscience |
Publication Date: | 2018 |
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. |
URI: | http://hdl.handle.net/11375/23747 |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Description | Size | Format | |
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Mancini_Steven_J_2018August_MSc.pdf | 6.71 MB | Adobe PDF | View/Open |
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