University of Texas Health Science Center San Antonio

Astrocyte Control of Toxin-Mediated Neuron Death: Role of the Gamma-Glutamyl Path

George Henderson, Ph.D.
hendersong@uthscsa.edu

Project Description

This grant will fund a study of toxin-mediated oxidative stress as a trigger that ultimately commits neurons to apoptotic death. The event can be associated with decreased cell glutathione (GSH) and cell death is mitigated by augmenting neuron GSH. An understanding of this neuroprotective pathway, especially its regulatory components and species comparisons, could ultimately lead to novel clinical interventions for devastating neurodegenerative disorders as well as establish accurate model systems. The overall hypothesis of this grant is that within the astrocyte-neuron axis, there is a highly effective, regulated pathway consisting of components which can enhance neuron GSH homeostasis in response to Parkinson's Disease-producing environmental toxins, thereby minimizing death of neurons. However, there are exposure patterns to these environmental cross-stressors which damage components of the pathways, thereby impairing its neuroprotective capacity. Experiments will utilize two-photon excitation microscopy to determine toxin effects specifically in cortical astrocytes and neurons in the living brain. The proposal addresses a new system by which glial cells protect neurons from the toxic effects of environmental toxins. These toxins can cause neurons to die as a result of oxidative damage, and cells called astrocytes prevent this by maintaining neuron antioxidants.