Date of Award

2023

Degree Name

Biomedical Sciences

College

Joan C. Edwards School of Medicine

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Larry Grover, Committee Chair

Second Advisor

Dr. Richard Egleton

Third Advisor

Dr. Travis Salisbury

Abstract

In the USA and especially in WV, there has been a surge in the rise of opioid use disorder (OUD), and with it a rise in neonatal abstinence syndrome (NAS). What makes this rise in NAS so unfortunate is that the Medications for OUD (MOUD) do not prevent the development of NAS. Although the relationship between MOUD and NAS is still unclear, it is thought that buprenorphine, one of the main substances used to treat OUD in pregnant women, may feed into the development of NAS, which may affect mental and physiological development and cause other health problems. Via understanding the developmental impact of NAS, we hope to pave the way for future NAS treatments and a brighter future for the children of the USA.

The central hypothesis of this proposal is that developmental issues caused by prenatal buprenorphine exposure are due to reduced expression of white matter development proteins, such as NG2 and MBP, and changes in neuronal proteins such as Kif5A, and that these changes cause deficits in the white matter parts of the brain. To study this hypothesis, we used a rat in utero buprenorphine exposure model to investigate the impact of this opioid on the post-natal time course of protein expression in two white matter tracts, the optic nerve and cerebellum.

Preliminary Western blot analysis indicates that there is a significant interaction between post-natal age and treatment for multiple proteins involved in myelination. Both white matter tracks also showed significant increases of KiF5A late in post-natal development. This data indicates that in utero buprenorphine impacts white matter development promoting a change in the protein expression timelines. If these developmental changes are maintained throughout the life span, they could explain some of the issues associated with the long-term impact of NAS.

Subject(s)

Opioid abuse – Treatment.

Pregnant women – Drug use.

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