Title

The Mediation of Insulin on Combined Effects of Fetal Astrocytic Hypoxia and Zinc

Date of Award

2015

Degree Type

Thesis

Degree Name

Master of Science (MS)

First Advisor

Harold Komiskey, PhD

Second Advisor

Francis Jenney, PhD

Third Advisor

Valerie Cadet, PhD

Fourth Advisor

Abigail Hielscher, PhD

Fifth Advisor

Valerie Cadet, PhD

Abstract

Astrocytes, known for their role in maintaining CNS homeostasis, are also involved in many pathological conditions. Hypoxia, a common complication of maternal Diabetes Mellitus, is among the traumas alleviated by astrocytes. Zinc maintains a considerable presence in the brain, yet in physiological conditions high zinc concentration poses no threat to proper cell functioning. However, when combined with hypoxic assault, zinc can lead to astrocytic stress and cell death. This project was designed to address intrapartum hypoxia by determining if embryonic astrocytes can be treated with a pharmaceutical agent that is safe for pregnant women and fetuses (insulin) to prevent hypoxic cell damage and death. Two sets of day-18 hippocampal rat primary astrocytes were pre-treated with insulin before adding zinc sulfate; one set was then placed in a hypoxia chamber to compare against the normoxic set. Various laboratory assays to quantify NF-κB and complement component 3 (C3) were used to assess inflammatory stress of the cells. The hypoxic cell sets support a trend of higher insulin levels leading to lower release of the inflammatory markers. Amongst relatively consistent cell viability across all samples, insulin appeared to have a protective role against hypoxic assault, with or without zinc.

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