The purpose of this research is to evaluate the effect of NNC 26-9100, a selective somatostatin receptor 4 (sstr4) agonist on modulation of uptake of Amyloid beta peptide in microglial cells. As of 2019 an estimated 5.8 million Americans are suffering from Alzheimer’s disease and it continues to be a huge societal burden. Amyloid peptides and neurofibrillary tangles are the hallmarks of the disease. Information from the literature has provided evidence that microglia play a crucial role in the degradation of amyloid beta plaques through various enzymes like neprilysin, Insulin degrading enzymes. Based on the works of Fleisher-Berkovich et al.,2010 we have hypothesized that NNC 26-9100, a selective sstr4 agonist increases the phagocytosis of amyloid peptide by BV2 cells in a manner that is dependent on the inflammatory state of the cells. To carry out this research work we used BV2 cells, LPS and NNC 26-9100 . Bv2 cells are immortalized microglial cells that maintain most of the phagocytic abilities and were demonstrated to have sstr4 receptors. Our goal was to study the effect of NNC 26-9100 on the phagocytosis of amyloid peptide by BV2 cells. Before using the compound to observe this effect we conducted the cytotoxic effects of NNC 26-9100 on BV2 cells. From the results, we observed NNC had no effect on the apoptosis of cells(P > 0.05). To study the effect on phagocytosis we stimulated BV2 cells using lipopolysaccharide (LPS) to induce inflammatory condition and then treated the cells with NNC 26-9100. We let them incubate for 24 hours and then added FITC 1-42(amyloid peptide) and have collected the samples at time intervals of 30 minutes, 2hours and 24 hours of incubation and ran flow cytometry. Results showed that NNC increased the uptake of amyloid peptide in LPS treated cells at 2 hours and 24 hours significantly (P < 0.05). To see the internalization of the amyloid peptide by BV2 cells we prepared slides and took images on confocal microscope. Overall, we were able to prove that NNC 26-9100 increased the phagocytosis of amyloid peptide by BV2 cells. The downstream events that upregulate the phagocytosis are not exactly known and yet to be identified. Some of the possible mechanisms can receptor mediated phagocytosis or endocytosis. In the future, more work must be done in this area. If NNC 26-9100 as assumed causes receptor mediated phagocytosis of amyloid peptide, then this would be a novel pharmacological approach to treat Alzheimer’s disease.
|Commitee:||witt, Ken, Nieto, Marcelo|
|School:||Southern Illinois University at Edwardsville|
|School Location:||United States -- Illinois|
|Source:||MAI 81/6(E), Masters Abstracts International|
|Keywords:||Alzheimer's disease, Dementia, Microglial modulation, Microscopy, NNC 26-9100, Phagocytosis|
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