Year of Award
Doctor of Philosophy (PhD)
Other Degree Name/Area of Focus
Integrative Microbiology and Biochemistry, Cellular and Molecular Biology
Department or School/College
Department of Chemistry and Biochemistry
Richard Bridges, Mark Grimes, Jesse Hay, Leonard Evans, Michael Kavanaugh
astrocytes, excitatory amino acid transporters, NMDA receptor, prion protein
University of Montana
Prion protein (PrP) is expressed on a wide variety of cells and plays an important role in the pathogenesis of transmissible spongiform encephalopathies. However, its normal function remains unclear. Mice that do not express PrP exhibit deficits in spatial memory and abnormalities in excitatory neurotransmission suggestive that PrP may function in the glutamatergic synapse. Here we show that transport of D-aspartate, a non-metabolized L-glutamate analog, through excitatory amino acid transporters (EAATs) was faster in astrocytes from PrP knockout (PrP KO) mice than in astrocytes from C57BL/10 SnJ wildtype (WT) mice. Experiments using EAAT subtype-specific inhibitors demonstrated that in both WT and PrP KO astrocytes, the majority of transport was mediated by EAAT1. Furthermore, PrP KO astrocytes were more effective than WT astrocytes at alleviating L-glutamate-mediated excitotoxic damage in both WT and PrP KO neuronal cultures. Thus, in this model, PrP KO astrocytes exerted a functional influence on neuronal survival and may therefore influence regulation of glutamatergic neurotransmission in vivo.
Pathmajeyan, Melissa Selvy, "Influence of Prion Protein Expression on Function of Excitatory Amino Acid Transporters in Mouse Primary Astrocytes" (2010). Graduate Student Theses, Dissertations, & Professional Papers. 577.
© Copyright 2010 Melissa Selvy Pathmajeyan