An examination of the noninflammatory role of astrocytes in glutamate excitotoxicity in SOD1 G93A ALS mouse model
Jordan, Kathleen Anne
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Astrocytes can be found between the vascular and neuronal elements of the central nervous system, where they take up and release molecules in order to maintain a homeostatic microenvironment for optimal neuron growth. Dysregulation of these astrocyte functions can lead to neuronal depolarization, hyperexcitability, excitotoxicity and subsequent neuronal death, characteristic of Amyotrophic Lateral Sclerosis (ALS). We hypothesize that the levels of glutamate and glutamate transporters in astrocytes increase over ALS disease progression and contribute to motor neuron death. Applying inclusion and exclusion criteria to a database comprising findings from over 2,000 papers resulted in data from over 60 papers. Data measuring glutamate concentrations and glutamate transmitter levels from SOD1 G93A (superoxide dismutase-1 glycine 93 to alanine) transgenic ALS mouse models were normalized to wild-type mice and graphed over time. We perform meta-analysis, correlation analysis, and survival analysis to determine the role of astrocytic glutamate regulation in disease progression. We demonstrate that GTL-1, GluR-1, and GluR-2 levels from astrocytes decrease over time. We propose that this trend may be associated with increased extracellular glutamate concentrations and the cellular attempts to maintain homeostasis. The findings of this analysis will give insight into the non-inflammatory role of astrocytes in the pathophysiology of ALS.