Differential Levels of Glutamate Dehydrogenase 1 (GLUD1) in Balb/c and C57BL/6 Mice and the Effects of Overexpression of the Gene on Glutamate Release in Striatum
Kevin N Hascup,
Xiaodong Bao,
Erin R Hascup,
Dongwei Hui,
Wenhao Xu,
Francois Pomerleau,
Peter Huettl,
Mary L Michaelis,
Elias K Michaelis,
Greg A Gerhardt
Affiliations
Kevin N Hascup
Anatomy and Neurobiology, Center for Microelectrode Technology, Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Kentucky, College of Medicine, Lexington, KY, U.S.A.
Xiaodong Bao
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, U.S.A.
Erin R Hascup
Anatomy and Neurobiology, Center for Microelectrode Technology, Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Kentucky, College of Medicine, Lexington, KY, U.S.A.
Dongwei Hui
Higuchi Biosciences Center, University of Kansas, Lawrence, KS, U.S.A.
Wenhao Xu
Department of Microbiology, University of Virginia Health System, Charlottesville, VA, U.S.A.
Francois Pomerleau
Anatomy and Neurobiology, Center for Microelectrode Technology, Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Kentucky, College of Medicine, Lexington, KY, U.S.A.
Peter Huettl
Anatomy and Neurobiology, Center for Microelectrode Technology, Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Kentucky, College of Medicine, Lexington, KY, U.S.A.
Mary L Michaelis
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, U.S.A.
Elias K Michaelis
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, U.S.A.
Greg A Gerhardt
Anatomy and Neurobiology, Center for Microelectrode Technology, Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Kentucky, College of Medicine, Lexington, KY, U.S.A.
We have previously shown that overexpression of the Glud1 (glutamate dehydrogenase 1) gene in neurons of C57BL/6 mice results in increased depolarization-induced glutamate release that eventually leads to selective neuronal injury and cell loss by 12 months of age. However, it is known that isogenic lines of Tg (transgenic) mice produced through back-crossing with one strain may differ in their phenotypic characteristics from those produced using another inbred mouse strain. Therefore, we decided to introduce the Glud1 transgene into the Balb/c strain that has endogenously lower levels of GLUD1 (glutamate dehydrogenase 1) enzyme activity in the brain as compared with C57BL/6. Using an enzyme-based MEA (microelectrode array) that is selective for measuring glutamate in vivo , we measured depolarization-induced glutamate release. Within a discrete layer of the striatum, glutamate release was significantly increased in Balb/c Tg mice compared with wt (wild-type) littermates. Furthermore, Balb/c mice released approx. 50–60% of the amount of glutamate compared with C57BL/6 mice. This is similar to the lower levels of endogenous GLUD1 protein in Balb/c compared with C57BL/6 mice. The development of these Glud1 -overexpressing mice may allow for the exploration of key molecular events produced by chronic exposure of neurons to moderate, transient increases in glutamate release, a process hypothesized to occur in neurodegenerative disorders.
