James Madl

Faculty Biomedical Sciences

233 Physiology


About James

Both glutamate toxicity and oxidative stress may contribute to the pathogenesis of many CNS diseases. We are currently investigating the mechanisms by which oxidative stress may contribute to glutamate toxicity in mercury toxicity, epilepsy, and glaucoma. Glutamine synthetase is an important enzyme in glutamate metabolism that is very vulnerable to loss due to oxidative stress. Loss of glutamine synthetase leads to the rapid loss of neurotransmission. We have found that oxidative stress may induce the loss of glutamine synthetase and epilepsy in sea lions exposed to the environment toxin domoic acid. This may then cause glutamate to accumulate in the extracellular fluid and overstimulate neurons, leading to epilepsy and neuronal cell death. Moreover, the glutamine synthase that is normally found in glial cells may be mistakenly expressed in neurons in these sea lions, contributing to CNS dysfunction. We are currently investigating the induction of oxidative stress and loss of glutamine synthetase in several diseases including domoic acid toxicity in seals and sea lions, mercury toxicity in seals and sea lions, and glaucoma in dogs and other mammals. We use primarily immunohistochemical techniques to look for markers of oxidative stress in different cell types as well as changes in the distribution of glutamine synthetase and glutamate. We believe these studies will provide a better understanding of how environmental toxins cause CNS disease in threatened species including seals and may lead to more effective therapies including the use of antioxidants.


PhD, University of Minnesota, 1988DVM, University of Minnesota, 1983MS, University of Minnesota, 1979BS, Lake Superior State College, 1975

Research Specialty

Neurotransmitter Release in Central Nervous System Disease


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