Title

An in vitro model of Alzheimer's disease using streptozotocin and glucose to test the ability of metformin and insulin to alleviate neurodegeneration.

Author

Monal Mehta

Date of Award

5-1-2015

Document Type

Thesis

School

College of Liberal Arts

Degree Name

Bachelor in Arts

Abstract

Alzheimer's disease (AD), a neurodegenerative disease, leads to a decline in memory and other mental abilities severe enough to interfere with everyday activity. Recent research has found increased risk of developing AD in the presence of Type 2 Diabetes Mellitus (T2DM). Increased blood glucose levels have been positively correlated with accelerated cognitive decline, and growing evidence suggest defective insulin signaling pathways within the AD brain. In this study, embryonic cortical neurons were cultured and treated with streptozotocin (STZ) and high levels of glucose in order to produce a neurodegenerative model of AD. MTS assays were used to assess cell viability. Combination of glucose and STZ led to significantly more toxicity than in conditions of only STZ (p < 0.05). Next, metformin and insulin, two agents currently used to combat high glucose levels in diabetic patients, were used separately and in conjunction to test their abilities in relieving neuronal toxicity. As expected, insulin, which is thought to act as a growth factor, led to a significant decrease in toxicity in all experiments (p < 0.05). Administration of a 24 hour metformin pre-treatment to 130 mM glucose led to significantly less neuronal toxicity than without a pre-treatment (p = 0.012). Overall, there were no consistent observable effects of STZ or Metformin. Future experiments will aim to determine the mechanisms of action of metformin, STZ, and how metformin pre-treatment is able to exert its beneficial effects.