Major and Classification
Biomedical Engineering
Faculty Mentor
Michael W. Jakowec, Ph.D.
Department
Viterbi School of Engineering
McNair Project
“Altered NMDA Expression with Treadmill Exercise in the MPTP-Lesioned Mouse Model of Basal Ganglia Injury”
Project Abstract
Parkinson’s disease (PD) is an age-related neurodegenerative disorder affecting 1-2% of adults aged 60 and older. The neuropathology of PD is marked by the selective-loss of dopaminergic neurons in the substantia nigra region of the basal ganglia, an important center for motor movement in the brain. Exercise has been shown to alleviate motor dysfunction symptoms in individuals with PD as well as altering AMPA-type glutamate receptor subunit expression in the MPTP mouse model of PD. In this study NMDA receptors were investigated, another class of glutamatergic receptors involved in neuroplasticity, with the hypothesis that the NR2B expression would decrease in exercised mice lesioned with MPTP. Male C57BL/6 mice (n=17) were used for this study, half of which were lesioned with the neurotoxin MPTP in order to model PD. The four experimental groups were: exercised (n=4) and non-exercised (n=5) saline treated mice and exercised (n=5) and non-exercised (n=3) mice lesioned with MPTP. Following the 6-week exercise paradigm, brains of all mice were harvested, the CPu region of the basal ganglia was dissected, and NMDA receptor subunit expression was analyzed by western immunoblotting. We found that mice lesioned with MPTP that underwent the exercise paradigm had a decrease in the NR2B subunit relative to the control MPTP group. Mice lesioned with MPTP that did not undergo the exercise paradigm showed an increase in NR2B relative to the saline group. The NR2B subunit expression increased significantly for mice treated with saline that underwent the exercise paradigm relative to the saline, non-exercised group. The expression of a different NMDA subunit, NR1, is in the process of being quantified and analyzed. We conclude that these changes in subunit expression suggest a role for NMDA receptors in exercise-induced neuroplasticity for repairing brain function, specifically in the damaged basal ganglia. Future studies can build on these data with the goal of possibly restoring the subunit expression of NMDA and AMPA receptors to that of a healthy basal ganglia in individuals suffering from PD.