The Role of Drosophila Perisynaptic Glial Cells in Glutamate Regulation

Open Access
Author:
Strauss, Alexandra Lee
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Richard W Ordway, Thesis Supervisor
  • Stephen Wade Schaeffer, Honors Advisor
Keywords:
  • glia
  • Drosophila
  • glutamate regulation
Abstract:
In the nervous system, an overabundance of the neurotransmitter glutamate, termed excitotoxicity, can lead to neurodegeneration and neurological disease. Our genetic analysis has focused on the roles of glial cells in regulating extracellular glutamate by examining the contributions of two glial proteins: dEAAT1, a glutamate transporter, and Glutamine Synthetase (GS2), an enzyme that converts glutamate to glutamine. Aberrant synaptic function, glutamate excitotoxicity and neurodegeneration may occur when proteins in glial cells, including dEAAT1 and GS2, do not regulate extracellular glutamate properly. Our studies in the Drosophila genetic model system employ in vivo RNA interference (RNAi) methods to reduce (knock down) the function of specific genes expressed in glial cells. Transgenic Drosophila lines in which glial dEAAT1 is knocked down exhibit severe neurodegeneration resulting in paralysis and tremors. On this basis, we have performed a genetic screen for new mutations that can suppress these neurodegenerative phenotypes with the goal of identifying novel molecular mechanisms which may provide protection against neurodegeneration. An exciting new suppressor mutant has been isolated and its genetic characterization is currently under way. In our analysis of GS2, we have generated transgenic lines permitting knockdown of GS2 in glia and have examined the resulting phenotypes. The GS2 knockdown has been instrumental in identifying perisynaptic glial cells involved in tripartite synapses in the Drosophila PNS. Our genetic analysis of these evolutionarily conserved mechanisms is expected to provide new insights into mechanisms of glutamate regulation in neurological health and disease.