Pharmacological manipulation of the glutamate transporter system in health and disease

Wilkie, Crystal M. (2019) Pharmacological manipulation of the glutamate transporter system in health and disease. Masters thesis, Memorial University of Newfoundland.

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Abstract

Glutamate transporter-1 (GLT-1) is the main glutamate transporter in the brain. Dysfunctional GLT-1 has been suggested to cause glutamate uptake impairments in Huntington disease (HD). It is thought that simply increasing GLT-1 expression can increase glutamate uptake in the brain. However, the functional effect of increasing GLT-1 expression in HD or the healthy brain has not been studied. We increased GLT-1 expression using two compounds, ceftriaxone and LDN/OSU-0212320 (LDN), and used the iGluSnFR technique to visualize glutamate dynamics in real-time. We found an impairment in glutamate uptake in the HD hippocampus in mice that was surprisingly not alleviated by ceftriaxone treatment. Furthermore, we found that increasing GLT-1 expression through ceftriaxone or LDN treatment in the healthy brain had no effect on glutamate uptake. These results suggest that increasing glutamate uptake is much more complex than just increasing GLT-1 expression.

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