The aim of this thesis is to evaluate the impact of somatostatin receptor subtype-4 (SSTR4) actions on microglia cell viability, towards the understanding and advance of pharmacological treatments for Alzheimer’s disease (AD). As of March 2016, there were 5 million people living in the United States with AD. Current drugs for AD have highly variable effects from patient to patient and are palliative at best. This thesis project focuses on the study of the BV2 cell line and the compound NNC 26-9100 (NNC). BV2 cells are immortalized microglial cells that maintain most of their morphology. The data collected suggests that BV2 cells can phagocytize amyloid-? peptides (A?), respond to lipopolysaccharide (LPS), and have the somatostatin receptor subtype-4 (SSTR4). NNC is a selective agonist of the SSTR4 and we have found that it causes BV2 cells to increase in number. The effects of NNC were able to be reduced with a somatostatin receptor pan-antagonist, cyclosomatostatin, and the adenyl cyclase activator forskolin. NNC can alter BV2 numbers by binding to the SSTR4, creating an intracellular cascade that results in the inhibition of adenyl cyclase and an increase in cell count. Collectively, a potential therapeutic mechanism for AD is increasing the number of microglial cells to increase both amyloid beta (A?) phagocytosis and degradation of A? by neprilysin.
|Advisor:||Schober, Joseph M.|
|Commitee:||De Meo, Christina, Witt, Ken|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 56/04M(E), Masters Abstracts International|
|Subjects:||Cellular biology, Biochemistry, Pharmacy sciences|
|Keywords:||Alzheimer's disease, Increased microglial survival, Microglia, Nnc 26-9100, Somatostatin subtype-4 agonist|
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