Translational neuroimaging of the young pig: Investigating sex-specific and environmental influences on neurodevelopment

Across the developmental field of neuroscience, the use of biomedical animal models is crucial for understanding the biological mechanisms and functional properties of the brain. However, selecting the proper animal model can be a daunting task when trying to achieve a balance of translational power and logistical feasibility. It is well known that non-human primates are the closest human developmental relative, but the logistical and ethical challenges encountered can make research near impossible. Therefore, for decades, the domestic pig has been utilized as a highly advantageous alternative due to the many neuroanatomical and gastrointestinal similarities with humans. Although many tools and resources have been developed for the pig, much ambiguity remains in how close in proximity pigs are to humans and the early developmental trends that are to be expected. Thus, the work in this dissertation aims to extend the translational power of the domestic pig in the developmental field, examine the effects of sex on brain development, and investigate early life environmental influences such as nutrition and gastro-inflammatory conditions. Specifically, the effects of nutritional supplementation of human milk oligosaccharides, Bifidobacterium longum subspecies infantis Bi-26, and encapsulated tributyrin on neurodevelopmental outcomes as assessed with neuroimaging were investigated in young pigs. Through this work we have determined that the domestic pig is the next closest species to human after non-human primates in terms of early development. Additionally, we report that there are minimal macrostructural and microstructural differences between sexes at an early stage of development and that axial and mean density as derived from diffusion tensor imaging predict myelin content in the hippocampus. In terms of environmental influences, dietary prebiotic and probiotic supplementation elicited minimal structural differences as determined from anatomical, diffusion, and myelin-specific scans. Furthermore, it was determined that early-life gastrointestinal inflammatory conditions, specifically ulcerative colitis, influence brain development by altering myelination concentrations, yet encapsulated tributyrin could not ameliorate these effects. In general, our results highlight the developmental proximity of the pig, the similar neurodevelopmental trajectories between sexes of the domestic pig, the limited developmental differences associated with nutritional supplementation, and the impact of early life inflammatory conditions. Overall, the work completed bolsters the domestic pig as an advantageous developmental preclinical model and provides a general framework for factors that should be taken into consideration during developmental research.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Neuroscience

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Sutkus, Loretta Teresa

Contributors dc:contributor

• Dilger, Ryan N
• Sutton, Brad P
• Lam, Fan
• Anderson, Aaron T

• neurodevelopment
• neuroimaging
• biological sex differences
• environmental influences
• nutrition
• porcine

Statement dc:rights

• Copyright 2025 Loretta Sutkus

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129417

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129417