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ORCID

https://orcid.org/0000-0001-6299-3384

Access Type

Open Access Thesis

Document Type

thesis

Embargo Period

9-1-2020

Degree Program

Public Health

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2020

Month Degree Awarded

September

Abstract

As reported by the CDC, birth defects remain a common occurrence in the United States, with malformations originating in many places in the developing organism. Furthermore, the etiology of many of these defects remain unknown, with some factors consisting of genetics, environmental pollutants and teratogens. In our study, we examined whether insults by teratogenic agents, ethanol in particular, can be mitigated by hyperpolarizing agents acting to restore the cell’s potential. We first evaluated whether three hyperpolarizing drugs (Lamotrigine, Gabapentin, and Ivermectin) induced teratogenic effects on CD-1 mice and found that Ivermectin induced craniofacial malformations, and exposure to Lamotrigine and Gabpentin resulted in limb defects in the offspring. For the second part of our study, pregnant CD-1 mice were orally dosed with Lamotrigine or Gabapentin from gestational day (GD) 0 till parturition. On GD 8, we exposed females to one hit of ethanol, creating four treatment groups: Vehicle, EtOH only, Lamotrigine + EtOH and Gabapentin + EtOH. We evaluated a variety of different endpoints: gestational outcomes, maternal outcomes, neonatal outcomes, behavioral outcomes in pups at prepuberty, and changes in brain weight, shape, and morphology. We observed that both Gabapentin and Lamotrigine, although in varied ways, mitigate some of the perturbations resulting from ethanol, but not all. Our study provides a preliminary, but insightful, look into the role of hyperpolarizing agents on teratogenic insults induced by ethanol. It highlights the future directions of research which include, but are not limited to, understanding the mode of action through which teratogens alter individual cell behavior and the interactions between hyperpolarizing agents on the cell’s potential when this alteration occurs.

DOI

https://doi.org/10.7275/17648171

First Advisor

Laura N. Vandenberg

Second Advisor

Alicia R. Timme-Laragy

Third Advisor

Timothy E. Ford

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