The Impact of Methylenetetrahydrofolate Reductase (MTHFR) Deficiency in a Paraquat Mouse Model of Parkinson’s Disease

The cause of Parkinson's disease (PD) remains unknown. Environmental toxicants such as paraquat have been linked to the characteristic dopaminergic (DA) neurodegeneration in the substantia nigra (SN); nutrition may also play a role. A common polymorphism (677C>T) in methylenetetrahydrofolate reductase (MTHFR), a folic acid metabolism enzyme, is associated with increased PD incidence. Using a mouse model that mimics this polymorphism, this study aimed to determine whether MTHFR deficiency leads to enhanced degeneration in a paraquat PD model. Male 3-month-old Mthfr+/+ and Mthfr+/- mice received paraquat or saline injections. Mthfr+/- mice demonstrated motor and a trend for memory impairment compared to Mthfr+/+ mice. No differences in SN DA neuron numbers or antioxidant activity were seen, however, increased oxidative stress and antioxidant activity were observed within the dorsal striatum of Mthfr+/- mice. These results suggest potential enhanced vulnerability to paraquat due to MTHFR deficiency through changes in such processes within this region.

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

2018

Author dc:creator

• Murray, Lauren Krystina

Statement dc:rights

• Copyright © 2018 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/2018-13371

OAI identifier oai:identifier

oai:carleton.scholaris.ca:20.500.14718/39113