| |
| author | Lindsay Jeanne Pearce |
| title |
Allosteric Modulation of mGlu4 Metabotropic Glutamate Receptors is Protective Against NMDA Induced Toxicity in Primary Neuronal Cell Culture
|
| abstract | For many of the key mental processes that occur in the brain daily, the brain relies on the regulation of glutamate, the primary
excitatory neurotransmitter. As the primary excitatory neurotransmitter in the brain, about 50% of cortical synapses are dedicated to glutamate signaling (Danysz and
Parsons 2012). Due to its high prevalence, dysregulation of the glutamate system can contribute to the development of several neurodegenerative diseases, including
Alzheimer's Disease. While glutamate blockers are prescribed as potential treatment for Alzheimer's Disease, this treatment has had only minimal impact on patient
cognition and no impact on patient progression. One area of research focuses on allosteric modulation of metabotropic glutamate receptors, specifically mGlu4, where
prior research establishes activation of this receptor to be protective in vitro (Bruno et al., 2000). This research uses two compounds, RD82 and RD87, both of
which are allosteric modulators of mGlu4, synthesized by Dr. Ronald Doll's group at Drew University, to assess their protective abilities against induced toxicity in
primary neuronal cell cultures. In this research, we used MTS assay, immunocytochemistry, and intracellular calcium assays to assess the protective abilities of RD82
and RD87 in cultures exposed to glutamate and NMDA induced toxicity. Using the combined results of MTS assay and immunocytochemistry, we found that RD82 is protective
against induced toxicity, while a pilot study of RD87 did not demonstrate protective abilities. Following confirmation of activity, RD82 was used for a pilot study to
address the hypothesis that RD82's mechanism of action could involve mediating calcium levels. |
| school | The College of Liberal Arts, Drew University |
| degree | B.A. (2017) |
| advisor | Roger Knowles |
| committee | Sarah Abramowitz
Ronald Doll |
| full text | LJPearce.pdf |
| |
