Virginia Via Research Day Book 2026

21 MATERNAL STIMULATION WITH IFN- γ LIMIT S VALP ROIC ACID INDUCED GENE EXPRESSION CHANGES IN MURINE NEURAL TUBES Medical Student Research Biomedical

Kayah Tucker 1 , OMS II; Murali K. Mallela 2 , PhD; Terry C. Hrubec 1,2 , DVM, PhD Corresponding author: ktucker@vcom.edu 1. VCOM-Virginia, Blacksburg, Virginia 2. Virginia-Maryland College of Veterinary Medicine, Virginia Tech Neurological disorders categorized as neural tube defects (NTDs) are a collection of congenital brain and spinal cord malformations, such as spina bifida, anencephaly, myelomeningocele, meningocele, and tethered spinal cord syndrome. Every year, NTDs affect ~ 300,000 newborns globally and ~ 3,000 pregnancies in the United States alone.1, 2 Researchers concur the precise cause of NTDs to be multifactorial through complex interplay between genetics, nutrition, and environmental factors. Valproic acid (VA), a γ-aminobutyric acid (GABA) analog used to treat seizures and mood disorders, is a known teratogen contributing to NTDs.3 Maternal immune Stimulation (MIS) during the periconceptual period with a variety of immune stimulants reduces birth defects, including VA-induced NTDs. This study examines the effect of MIS on cell signaling pathways in the developing embryo. It is hypothesized that MIS

normalizes dysregulated signaling pathways within embryos exposed to VA, reducing the formation of NTDs. Female CD-1 mice were immune simulated pre-breeding with IFN-γ and exposed to VA on day 8 of gestation, the critical period for neural tube closure. Embryonic heads were collected on day 8.5 and 9.5 for RNA isolation and gene expression analysis. Gene expression was determined using a Signal Transduction Profiler PCR array. NTDs decreased from 45.3 to 21.2 % /liber with MIS. Signal transduction gene expression was normalized with VA+IFN-γ in day 8.5 embryonic heads and in day 9.5 heads with closed neural tubes. At present, the mechanisms for how MIS regulates signal transduction in the embryo are unknown, but we have identified GM-CSF and IFN-γ as possible effectors of MIS; specifically, we recognize GM-CSF, IL-6, and IL-10 in preventing NTDs. The next phase in

this study is to further clarify MIS influence on gene expression in specific cell signaling pathways within VA-exposed embryos. Our findings have the potential to determine a molecular mechanism for MIS in general and the prevention of VA-induced NTDs specifically.

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