Milk fat globule membrane promotes brain development in piglets by enhancing the connection of white matter fiber trace

Abstract

Introduction: Brain development during infancy is crucial for later health and development. Although Milk Fat Globule Membrane (MFGM) has been demonstrated to enhance brain development, further investigation is needed to determine the optimal dose.

Methods: In this study, 80 piglets aged 2 days were randomly assigned to four groups: Control group, MFGM-L (1.74 g MFGM per 100 g diet), MFGM-M (4.64 g MFGM per 100 g diet), and MFGM-H (6.09 g MFGM per 100 g diet). Daily body weight and milk intake of the piglets were recorded until 31 days postnatal. Learning and memory abilities were evaluated using the spatial T-maze test on day 15. MRI analysis was conducted to assess functional and structural changes in brain tissues. Additionally, mRNA and protein expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NTF-3) in the hippocampus and prefrontal cortex were evaluated.

Results: The results indicated that the MFGM supplemented diet significantly improved the accuracy of the piglets in the T-maze test, with the MFGM-L group exhibiting the best performance. MRI showed no volumetric differences in the gray and white matter between the groups. However, the fractional anisotropy in the left and right hippocampus of piglets in the MFGM-L group was significantly higher than in the other three groups. Furthermore, there was a strong correlation between the accuracy of the T-maze test and hippocampal fractional anisotropy.

Discussion: The MFGM supplemented diet also increased the expression of BDNF in the cerebral cortex. However, the changes in BDNF were not consistent with the results of the T-maze test. In conclusion, adding 1.74 g MFGM per 100 g diet can significantly improve neonatal piglets' learning and memory abilities, potentially by enhancing the connection of white matter fiber bundles in the brain.

Keywords: BDNF; MFGM; fractional anisotropy (FA); infant diet; memory-improvement.

Figure 1

Timeline of the experimental procedure. Piglets aged 2 days postnatal (day 1) were brought to the animal facility. They were fed with a nutritionally complete, customized milk replacer for a month. The T-maze tests were performed from day 15 to 23 for spatial learning and memory assessment. MRI was conducted on day 29. The piglets were all sacrificed on day 30.

Figure 2

T-maze performance of piglets aged 16–24 days. Correct rate (A); Correct latency (B); Proportion correct rate (C); Days of qualification (D); Non-qualified rate (E); The earliest qualified days (F). n = 20 in Control and MFGM-H groups; n = 19 in MFGM-L and MFGM-M groups. Data were presented as mean ± SEM.

Figure 3

The volume and fractional anisotropy of white matter and gray matter determined by MRI. Representative images of white matter (A) and gray matter (B) determined by VBM. The volume of White matter (C), Gray matter volume (D), Representative image of Fractional anisotropy in of the whole brain, corpus callosum, and hippocampus (E). Fractional anisotropy analysis of the whole brain (F), corpus callosum (G), left hippocampus (H), and right hippocampus (I). n = 20 in Control and MFGM-H groups; n = 19 in MFGM-L and MFGM-M groups. Data were presented as mean ± SEM.

Figure 4

Correlations between FA and correct rate. Correlations between FA in the whole brain (A), corpus callosum (B), left hippocampus (C), right hippocampus (D), and correct rate (AUC). n = 20 in Control and MFGM-H groups; n = 19 in MFGM-L and MFGM-M groups. Data were presented as mean ± SEM.

Figure 5

The relative expression of BDNF and NTF-3 in the brain. The expression of BDNF mRNA in the hippocampus (A) and Prefrontal cortex (PFC) (B) relative to β-actin. Control (n = 15), MFGM-L (n = 18), MFGM-M (n = 13), MFGM-H (n = 16); The protein expression of BDNF and NTF-3 in the hippocampus in each group (C,D). Data were presented as mean ± SEM.