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

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Creator: 

Bellevue, Shannon

Date: 

2016

Abstract: 

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.

Subject: 

Neuroscience

Language: 

English

Publisher: 

Carleton University

Thesis Degree Name: 

Master of Science: 
M.Sc.

Thesis Degree Level: 

Master's

Thesis Degree Discipline: 

Neuroscience

Parent Collection: 

Theses and Dissertations

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