The major objective of this proposal is to elucidate the molecular basis of the neuropathology associated with nutritionally induced neuromuscular disorders. A secondary goal is to these nutritional deficiencies in animals into useful and valid models of specific human diseases. Zinc deficiency guinea pigs results in a peripheral neuropathy highly analogous to that associated renal disease in man and various idiopathic neuropathies. Copper deficiency in rats produces central nervous system pathology similar to that of Parkinson's disease and possibly Huntington's chorea. There are few animal models of the painful human neuropathies and in many cases, they are not appropriate for assessment of therapeutic drugs nor a model for study of the basic biochemical defects of the disease. Neither is there a valid rodent model of Parkinson's disease nor an established molecular basis for the low dopamine levels and neuronal death associated with the disease. We hypothesize that zinc plays a key role in the maintenance of plasma membrane structure and function and that a deficiency impairs membrane receptors and ion channel function. Biochemical assessment of ion channels and associated enzyme systems of peripheral nerves and the histopathology of these nerves and the motor end plates of zinc deficient animals constitutes one of two major thrusts of the project. The other thrust is development of a genetic strain of rats that give a consistent nervous system pathology in copper deficiency. This model will be used to probe the locomotor brain disorders that simulate those of Parkinson's disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Nutrition Study Section (NTN)
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University of Missouri-Columbia
Schools of Earth Sciences/Natur
United States
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