My primary area of research focuses on the neuroprotective effects of antioxidants in the rat model of Parkinson's disease. Parkinson's disease is a progressive neurodegenerative disorder in which resting tremor, muscular rigidity, bradykinesia (slowness of movement) and impaired postural reflexes predominate. It is observed in approximately 1% of the American population over the age of 55. The primary pathology of this disease is a degeneration of the "nigrostriatal pathway". This pathway originates in the substantia nigra of the midbrain and projects anteriorly to the striatum. As degeneration of this pathway progresses, there is a loss of dopamine neurons as well as depletion of dopamine metabolite levels in the striatum. Current available therapy relieves many of the symptoms in the early to middle stages of the disease but does not arrest or attenuate the advancement of the disease. Therefore, it is beneficial to identify possible alternative therapies in alleviating or inhibiting the progression of this debilitating neurodegeneration.
There is significant research implicating free radicals in the manifestation of neurodegenerative disorders such as Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. Therefore, it is reasonable to hypothesize that antioxidant therapies may be neuroprotective and reduce the progression of these diseases. Preliminary studies in my lab have proved promising. Selenium administration (2ppm) daily is able to protect 50%of substantia nigra dopamine neurons in the 6-OHDA nigral lesion rat. My students and I (in collaboration with Wayne Cass at the University of Kentucky) have also demonstrated significant protection of dopamine synthesis and metabolism in these nigral cells via HPLC analysis. Further investigation is under way to accurately define the scope of protection offered by antioxidants, such as alpha-tocopherol and selenium, in rats challenged with 6-OHDA induced degeneration of the nigrostriatal pathway.
Library of Congress CUR/NCUR Celebration
Hadeed NM and Fox CM. Dietary selenium may improve both fine motor and gross motor skills in the 6-hydroxydopamine rat model of Parkinson’s disease
Renninger J and Fox CM. The effect of Lansoprazole on microglial activation in a rodent model of Alzheimer’s disease
McCambridge T and CM Fox. Dietary selenium protects dopamine levels and may improve motor behavior in the 6-OHDA rat model of Parkinson’s disease,
Visram, KF and Fox CM. The effect of long term selenium exposure in the striatal 6-OHDA model of Parkinson’s disease: a cell survival and behavior study
Goodbred A. and Fox, C.M. Behavioral analysis of the neuroprotective effects of selenium in the 6-OHDA nigral lesion model.
Siegfried R, Varvarelis P and Fox CM. Selenium as a neuroprotective agent in the 6-OHDA striatal lesion model.
Varvarelis P, Siegfried R and Fox CM. Can the protection elicited by selenium in the 6-OHDA lesion model extend to aged Brown Norway/Fischer 344 rats?
Bowsher C and Fox CM. Intramuscular administration of GDNF into the rat masseter: a possible delivery site for retrograde transport to the substantia nigra.
Mueller S and Fox CM. Long term selenium administration as a protective agent in the 6-OHDA lesion model.
Drost M and Fox CM. Administration of selenium as a protective agent in the 6-OHDA nigral lesion model.