Dietary omega-3 fatty acid deficiency from pre-pregnancy to lactation affects expression of genes involved in hippocampal neurogenesis of the offspring

Abstract

Maternal n-3 PUFA (omega-3) deficiency can affect brain development in utero and postnatally. Despite the evidence, the impacts of n-3 PUFA deficiency on the expression of neurogenesis genes in the postnatal hippocampus remained elusive. Since postnatal brain development requires PUFAs via breast milk, we examined the fatty acid composition of breast milk and hippocampal expression of neurogenesis genes in n-3 PUFA deficient 21d mice. In addition, the expression of fatty acid desaturases, elongases, free fatty acids signaling receptors, insulin and leptin, and glucose transporters were measured. Among the genes involved in neurogenesis, the expression of brain-specific tenascin-R (TNR) was downregulated to a greater extent (∼31 fold), followed by adenosine A2A receptor (A2AAR), dopamine receptor D2 (DRD2), glial cell line-derived neurotrophic factor (GDNF) expression in the n-3 PUFA deficient hippocampus. Increasing dietary LA to ALA (50:1) elevated the ARA to DHA ratio by ∼8 fold in the n-3 PUFA deficient breast milk, with an overall increase of total n-6/n-3 PUFAs by ∼15:1 (p<0.05) compared to n-3 PUFA sufficient (LA to ALA: 2:1) diet. The n-3 PUFA deficient mice exhibited upregulation of FADS1, FADS2, ELOVL2, ELOVL5, ELOVL6, GPR40, GPR120, LEPR, IGF1 and downregulation of GLUT1, GLUT3, and GLUT4 mRNA expression in hippocampus (p<0.05). Maternal n-3 PUFA deficiency affects the hippocampal expression of key neurogenesis genes in the offspring with concomitant expression of desaturase and elongase genes, suggesting the importance of dietary n-3 PUFA for neurodevelopment.

Keywords: Breast milk; DHA; Desaturase; Hippocampus; Neurogenesis; n-3 PUFA deficiency.