Neurolathyrism is a human disease characterized by chronic lesions of the central nervous system leading to spastic paralysis of the legs and is caused by the consumption of the seeds of Lathyrus sativus as the sole diet source. As a result it annually causes the death of several hundred thousand persons in the southern region of the Soviet Union and India. The studies carried out in Dr. Sarma's laboratory have shown that the effect of the seeds are due to the presence of a neurotoxin, beta-n-oxalyl-L, alpha-beta-diaminopropionic acid (ODAP). The uptake of ODAP into the brain changes the regulation of glutamate and ammonia pools in brain tissue. Glutamate, ammonia and related metabolites serve the needs of energy metabolism, synthesis of neurotransmitter and inhibitory substances, and protein biosynthesis. We propose to determine which enzymes and transport mechanisms are affected by ODAP. We will seek: 1. A more detailed understanding of the neurotransmitter function of glutamate and its metabolism in the brain, which are still not well understood. ODAP will be a useful probe for these studies. 2. A better understanding of the destructive reactions involved in dysfunction and the pathological changes in the central nervous system characteristic of the disease. 3. A rational basis for the prevention, retardation and diagnosis of neurolathyrism.
NIH ExPorter
NIH ExPorter