Medicine and Health Sciences Commons^™

Differential Levels Of Glutamate Dehydrogenase 1 (Glud1) In Balb/C And C57bl/6 Mice And The Effects Of Overexpression Of The Glud1 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

Neuroscience Faculty Publications

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 …

Increased Mitochondrial Calcium Sensitivity And Abnormal Expression Of Innate Immunity Genes Precede Dopaminergic Defects In Pink1-Deficient Mice, Ravi S. Akundi, Zhenyu Huang, Joshua Eason, Jignesh D. Pandya, Lianteng Zhi, Wayne A. Cass, Patrick G. Sullivan, Hansruedi Büeler

Neuroscience Faculty Publications

BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²⁺ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice.

METHODS AND FINDINGS: Purified brain mitochondria of ^Pink1⁻/⁻ mice showed impaired Ca²⁺ storage capacity, resulting in increased Ca²⁺ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. …