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Microglial innate and adaptive immune function modulates disease pathology in and environmental pesticide model of Parkinson's disease

dc.contributor.authorRocha, Savannah M., author
dc.contributor.authorZabel, Mark, advisor
dc.contributor.authorTjalkens, Ronald B., advisor
dc.contributor.authorBouma, Jerry, committee member
dc.contributor.authorKading, Rebekah, committee member
dc.contributor.authorMoreno, Julie, committee member
dc.description.abstractParkinson's Disease (PD) is the world's foremost movement disorder with pathological features including loss of dopaminergic neurons (DAn) within the substantia nigra pars compacta (SNpc), chronic activation of glial cells, and the misfolding and aggregation of a-synuclein (a-syn). Compounding evidence gathered over the past two centuries suggests environmental exposures, genetics, and aging can induce complicated cell-to-cell interactions that evoke and facilitate chronic inflammatory states; but the role that individual glial cells, in particular microglia, have in the progression of disease remains unknown. Difficulties in recapitulating the three pathological hallmarks of PD underscore the need for better animal models. To address this gap in functional investigation, the studies herein provide, for the first time, an optimized environmental exposure model with the pesticide rotenone (2.5mg/kg/day) in murine, which has proven effective at mirroring DAn degeneration, gliosis and misfolded a-syn accumulation. The pathology observed was region-, time- and dose-dependent, emphasizing the importance of environmental exposure and associated PD diagnosis. The successful optimization of this exposure model has allowed for its implementation in transgenic mice, which was previously unfeasible. To determine microglial specific innate inflammatory reactions in the progression of PD, we targeted the inflammatory transcriptional regulator NF-kB by use of transgenic CX3CR1-Cre
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.publisherColorado State University. Libraries
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see
dc.subjectprotein misfolding
dc.subjectParkinson's disease
dc.titleMicroglial innate and adaptive immune function modulates disease pathology in and environmental pesticide model of Parkinson's disease
dcterms.rights.dplaThis Item is protected by copyright and/or related rights ( You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s)., Immunology, and Pathology State University of Philosophy (Ph.D.)


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