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Office: 233 Physiology Building
Phone: 970-491-7440
Fax: 970-491-7907
Email: James.Madl@ColoState.edu

James E. Madl, DVM, PhD

​Associate Professor, Department of Biomedical Sciences
Program in Molecular, Cellular and Integrative Neurosciences
Colorado State University

Education


PhD, University of Minnesota
DVM, University of Minnesota
MS, University of Minnesota
BS, Lake Superior State College

Research Interests -- Neurotransmitter Release in Central Nervous System Disease


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.

Representative Publications


For a complete list of publications, please visit: JE Madl PubMed

Chen C-T, Alyahya K, J.R. Gionfriddo, R.R. Dubielzig and JE Madl, 2008. Loss of glutamine synthetase immunoreactivity from the retina in canine primary glaucoma. Veterinary Ophthalmology 11(3):150-7.

Gionfriddo JR, Freeman K, Groth A,  Scofield VL, Alyahya K, and JE Madl, 2009. a-luminol prevents decreases in glutamate, glutathione and glutamine synthetase in the retinas of glaucomatous DBA/2J mice. Veterinary Ophthalmology 12(5):325-332

James E. Madl, Colleen Duncan, Jason Stanhill, Pei-Yi Tai, Terry Spraker, Frances M. Gulland, 2014.

Oxidative stress and redistribution of glutamine synthetase in California sea lions (Zalophus californianus) with domoic acid toxicosis. Journal of Comparative Pathology 150 (2-3): 306-15.

Thomas Chen, Juliet R. Gionfriddo, Pei-Yi Tai, Anna Novakowski, Khaleel Alyahya, and James E. Madl, 2014.

Oxidative stress in retinas of dogs with acute glaucoma. Veterinary Ophthalmology 17:1463-5224.

Kirkley KS; Madl JE; Duncan C; Gulland FM; Tjalkens RB, 2014. Domoic acid-induced seizures in California sea lions (Zalophus californianus) are associated with neuroinflammatory brain injury. Aquatic Toxicology 156C: 259-268.