Investigating the effect of stress on a mouse model for Parkinson’s disease

• Main Author: Yeo, Natalie
• Other Authors: Zoë Bichler
• Format: Final Year Project
• Language: English
• Published: 2017
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/72380
• Institution: Nanyang Technological University

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. Among the genes found to be mutated in PD, the LRRK2 (R1441G) mutation, frequent in the Basque country, shows high penetrance and has been used to generate a genetic mouse model for PD. With chronic stress known to aggravate dopaminergic neurodegeneration and motor dysfunction in PD rodent models, we aimed to study the effects of stress on the LRRK2 (R1441G) mouse model of PD. Mice were treated with neurotoxins (a mixture of paraquat and maneb, PQMB) and unpredictable chronic mild stress early in life. Locomotor activity, the number of dopaminergic neurons in the substantia nigra pars compacta (SNpc) at 16 months and hair cortisol levels at 9 months were assessed. Stress exacerbated behavioral deficits in PQMB-treated mice and the LRRK2 (R1441G) mutation showed no effect on SNpc dopaminergic neuron number. Cortisol levels revealed significantly lower baseline cortisol and a tendency towards dysfunctional stress management in LRRK2 (R1441G) mice. Our results imply that stress might play an important role in PD and that dysregulation of cortisol levels might be an early feature in PD. If confirmed, cortisol levels could be used as a biomarker to detect at-risk patients for early treatment.