Sex and LRRK2 Genotype Differences in Inflammation and Dopaminergic Neurodegeneration in a Multi-Hit Model of Parkinson's Disease

Parkinson’s disease (PD) is a multifactorial condition precipitated by environmental insults in conjunction with genetic vulnerabilities, sex differences, and aging. The objective of the current thesis was to explicate potential additive/synergistic effects of genetic LRRK2 anomalies and environmental risk factors as they pertain to motor behaviour, nigrostriatal dopaminergic degeneration, and neuroinflammation. Moreover, since the male sex represents a significant risk factor in PD, sexual dimorphisms were addressed. To achieve this, male and female mice bearing the G2019S-LRRK2 mutation were exposed to a systemic lipopolysaccharide+paraquat (LPS+PQ) neurotoxicant challenge. Contrary to expectations, no additive/synergistic effects were observed between the G2019S mutation and LPS+PQ exposure. In fact, male G2019S mice appeared to be protected from the degenerative effects of LPS+PQ at this age. Moreover, an unanticipated sex by treatment interaction was found, such that female mice displayed greater deficits in gait and loss in nigral TH+ neurons compared to males.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Master's

Discipline thesis:degree_discipline

Neuroscience

Grantor dc:publisher

Carleton University

Year dc:date.issued

2016

Author dc:creator

• Bellevue, Shannon

Statement dc:rights

• Copyright © 2016 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.

Language dc:language.iso

en

DOI

10.22215/etd/2016-11276

OAI identifier oai:identifier

oai:carleton.scholaris.ca:20.500.14718/39847