Date of Award
Master of Arts
A growing body of research suggests that dopaminergic cell death seen in Parkinson’s disease is caused by mitochondrial dysfunction. Oxidative stress, with subsequent generation of reactive oxygen species, is the hallmark biochemical product of mitochondrial dysfunction. The ketogenic diet has been found to enhance mitochondrial energy production, protect against reactive oxygen species-generated cell death, and increase adenosine, a purine that modulates dopamine activity. The current study evaluates the effects of a long-term (5-month) ketogenic diet on behavioral, neurochemical, and neuroanatomical measures in PINK1-KO rats, a new animal model of Parkinson’s disease. Both wild-type and PINK1-KO animals fed a ketogenic diet exhibited significantly higher blood beta-hydroxybutyrate levels. PINK1-KO animals fed a normal diet experienced a decrease in stride length and an increase in stride frequency over time which was absent in PINK1-KO animals fed a ketogenic diet. Animals fed the ketogenic diet had decreased tissue content of both adenosine and inosine in the nucleus accumbens, posterior caudate, hippocampus, and substantia nigra. Finally, immunohistochemical staining for tyrosine hydroxylase-positive cells in the substantia nigra suggest a ketogenic diet-induced protection of dopaminergic cell death. The results of the present study indicate that a long-term ketogenic diet may positively impact both motor and neuroanatomical correlates and alter neurochemical systems in a genetic rodent model of Parkinson’s disease.
Rubin, Jacob and Church, William H., "An Initial Analysis of a Long-Term Ketogenic Diet’s Impact on Motor Behavior, Brain Purine Systems, and Nigral Dopamine Neurons in a New Genetic Rodent Model of Parkinson’s Disease" (2016). Masters Theses. 23.
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