Abstract
Introduction: Osteopontin (OPN) is a whey protein found at high concentration in human milk and is involved in processes such as bone cell proliferation and differentiation. Milk OPN has shown to be involved in various aspects of development, including the immune system and gut health. However, the influence of dietary bovine milk OPN inclusion on brain and cognitive development has not been studied extensively until recently. This research examines whether dietary supplementation of bovine milk OPN supports brain and cognitive development in the translational pig model. Methods: From postnatal day (PND) 2 to 34, twenty-one intact male pigs were provided ad libitum access to one of two dietary treatments, a standard soy protein isolate-based milk replacer to serve as a control diet (n = 11) and the same base diet supplemented with bovine milk OPN to serve as a test diet (n = 10). In addition to growth and health outcomes, recognition memory was tested using the novel object recognition (NOR) task from PND 28 to 32, and magnetic resonance imaging was conducted at PND 34 to evaluate brain development. Results: No dietary effects were observed for growth performance or health indices. For the behavioral analysis, pigs that received the test diet exhibited shorter (p < 0.05) latency to the first object visited compared with pigs fed the control diet. Although the control group exhibited novelty preference, there was no difference in recognition index between dietary groups. Neuroimaging outcomes revealed increased (p < 0.05) relative brain volumes of the corpus callosum, lateral ventricle, left and right internal capsule, left and right putamen-globus pallidus, and right hippocampus, and right cortex in the test group. Diffusion tensor imaging revealed higher (p < 0.05) radial diffusivity in the corpus callosum and lower (p < 0.05) fractional anisotropy in pigs provided the test diet. Conclusion: Dietary supplementation of bovine milk OPN increased the relative volume of several brain regions and altered behaviors in the NOR task. Underlying mechanisms of bovine milk OPN influencing the development of brain structures and additional behaviors warrant further investigation.
Highlights
Osteopontin (OPN) is a whey protein found at high concentration in human milk and is involved in processes such as bone cell proliferation and differentiation
Previous research has shown that the difference in bioactive compounds, such as proteins, in human milk and infant formula may explain the difference between breast fed infants and formula-fed infants in growth, health outcomes, microbiome, and immunological development [4,5,6]
Seven pigs were excluded from collecting magnetic resonance imaging (MRI) and behavioral outcomes due to failure-to-thrive, so data from twenty-one pigs were used for subsequent analysis (n = 11 pigs in Control group and n = 10 pigs in OPN group)
Summary
Osteopontin (OPN) is a whey protein found at high concentration in human milk and is involved in processes such as bone cell proliferation and differentiation. This research examines whether dietary supplementation of bovine milk OPN supports brain and cognitive development in the translational pig model. In addition to growth and health outcomes, recognition memory was tested using the novel object recognition (NOR) task from PND 28 to 32, and magnetic resonance imaging was conducted at PND 34 to evaluate brain development. Despite continuous improvements of infant formulas to mimic the composition of human milk, growth, health, and neurodevelopment outcomes of formula-fed infants are different to those of breast-fed infants [3]. Previous research has shown that the difference in bioactive compounds, such as proteins, in human milk and infant formula may explain the difference between breast fed infants and formula-fed infants in growth, health outcomes, microbiome, and immunological development [4,5,6]. As a highly phosphorylated glycoprotein with an integrin binding sequence, OPN is synthesized in various tissues and exists in many different isoforms due to post-translational modulation and splicing of the protein
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