Parkinson’s Disease (PD), the second most common neurodegenerative disease worldwide, pathologically presents with the inclusion of Lewy bodies and dopaminergic cell loss in the brain. Lewy bodies are composed of aggregated a-synuclein protein, and although essential to our understanding of PD, not much is known about the native, pre-synaptic state of a-synuclein (a-syn). Due to its mostly synaptic local, immunostaining results in diffuse signal, ultimately providing little insight into the types of a-syn-resident cells. As a result, insight into a-syn expression driven cellular vulnerability has been difficult to ascertain. Using a knockin mouse model that localizes a-syn to the nucleus of cells by insertion of a nuclear localization signal into the a-syn gene locus (SncaNLS), we overcome visualization issues and map out the topography and cells-of-origin of a-syn in mice. I performed immunohistochemistry on SncaNLS mouse tissue to map out the endogenous distribution of a-synuclein in the brain. Using ilastik machine learning analysis, I determined regions with high a-syn expression, which were subsequently co- stained with cell-type specific markers to gain further topographical granularity. a-syn showed high expression in the olfactory bulb, hippocampus, cerebral cortex, substantia nigra and cerebellum. Within these structures, there was a high level of expression of a-syn in granule cells, pyramidal cells, mitral cells, and dopaminergic neurons. Taken together, the SncaNLS mouse serves as a tool to define an atlas of a-syn topography, potentially providing insight into cellular vulnerability in PD.
Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/44455 |
Date | 03 January 2023 |
Creators | Fisk, Zoe |
Contributors | Rousseaux, Maxime |
Publisher | Université d'Ottawa / University of Ottawa |
Source Sets | Université d’Ottawa |
Language | English |
Detected Language | English |
Type | Thesis |
Format | application/pdf |
Rights | Attribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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