Lipidomics Analysis Reveals the Effects of Docosahexaenoic Acid from Different Sources on Prefrontal-Cortex Synaptic Plasticity

Abstract

Background: Docosahexaenoic Acid (DHA) is an extensively used nutrition supplement in dairy food because of its beneficial effects on cognition. To find an effective DHA intervention for the synapses in the cortex during this period, this study aimed to use targeted lipidomics to evaluate the lipid composition of prefrontal-cortex (PFC) tissue in different DHA interference methods.

Methods: Analyzed samples were taken from interfering feeding Bama pigs (BPs) (3 months) fed with soybean oil (Group B), blended oil (Group M), naturally DHA-supplemented milk with blended oil (Group OM), and DHA from fish oil (FO) with blended oil (Group Y). We also examined the protein expression levels of BDNF, GAP43, and MBP.

Results: The lipidomics analysis identified 80 different related negative-ion lipid content and filtered the biomarker lipids in PFC tissue. We observed significant lipid composition changes between group Y and other groups, especially for content levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and sphingomyelin (SM). The same observations were made from mRNA and protein expressions related to lipid transportation, phosphatidylserine (PS) synthetase, and synaptic plasticity in PFC tissues between group Y and other groups, including the mRNA expression levels of CD36, BDNF, and PTDSS1. The analysis of protein expression levels showed that the metabolism mode of DHA intervention from FO benefited the PFC, PS metabolism, and PFC synaptic plasticity of infants.

Conclusions: The results highlight further prospects for the DHA intervention mode, which provides new routes for other studies on polyunsaturated-fatty-acid (PUFA) interference for infants.

Keywords: DHA intervention; PFC; lipid composition; lipidomics; synaptic plasticity.

Figure 1

Comparison of total lipid contents in PFC tissues from different groups: (A) Lipid contents in total. (B) PL content. (C) Total PC content. (D) Total PI content. (E) Total PS contents. (F) Total SHexCer contents. (G) Heatmap. (H) Chord plot. (I) Venn diagram Analysis. Data are shown as the mean ± SEM, n = 4. The significance of the differences was estimated by one-way ANOVA. a, b: Represent significant differences (p < 0.05). PC: phosphatidylcholine; PI: phosphatidylinositol; PS: phosphatidylserine; SHexCer: sulfated hexosyl ceramide.

Figure 2

The content levels of PC (A–E) and PE (F–J) in different groups. Data are shown as mean ± SEM, n = 3. The significance of the differences was estimated by one-way ANOVA. a, b: Represent significant differences (p < 0.05). PC: phosphatidylcholine; PE: phosphatidylethanolamine.

Figure 3

The content levels of PI (A–E), PS (F–L), SHexCer (M,N), and SM (O) in different groups. Data are shown as mean ± SEM, n = 3. The significance of the differences was estimated by one-way ANOVA. a, b: Represent significant differences (p < 0.05). PI: Phosphatidylinositol; PS: Phosphatidylserine; SHexCer: Sulfated hexosyl ceramide; SM: Sphingolipids.

Figure 4

Pathway analysis based on differential species: (A) B vs. Y. (B) M vs. Y. (C) OM vs. Y. The node colors (yellow and red) are based on p-values (Y-axis, where yellow indicates higher p values; red indicates lower p values), and the node size determines impact values of the pathway (X-axis, where the larger the size, the higher the impact score). Enrichment Analysis of the related node based on Sub_Class database: (D) B vs. Y. (E) M vs. Y. (F) OM vs. Y. Partial Correlation Network integrating related metabolic functions, displaying interactions and betweenness centrality. (G) B vs. Y. (H) M vs. Y. (I) OM vs. Y. PC: phosphatidylcholine; PI: phosphatidylinositol; PS: phosphatidylserine; SHexCer: sulfated hexosyl ceramide.

Figure 5

The mRNA expression (A–D) in PFC tissue from different groups. The protein expression (E–J) in PFC tissue from different groups. The PTDSS1 concentration (I) in PFC tissue from different groups. Data in (A–D,J) are shown as the mean ± SEM, n = 6. Data in (F–J) are shown as the mean ± SEM, n = 3. The significance of the differences was estimated by one-way ANOVA and Waller–Duncan. Different letters represent significant differences in protein contents in different lactation periods (p < 0.05). GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; BDNF: Brain derived neurotrophic factor; CD36: Thrombospondin receptor; PTDSS1: Phosphatidylserine synthase 1; PTDSS2: Phosphatidylserine synthase 2; BDNF: Brain-Derived Neurotrophic Factor; MBP: Myelin Basic Protein; GAP43: Growth-Associated Protein 43; SYP: Synaptophysin.