Low omega-6/omega-3 ratio in a maternal protein-deficient diet promotes histone-3 changes in progeny neural cells and favors leukemia inhibitory factor genetranscription

Omega-3 (n-3) fatty acids modulate epigenetic changes critical to genesis and differentiation of neural cells. Conversely, maternal protein-malnutrition can negatively modify these changes. This study investigated whether a low n-6/n-3 ratio in a maternal diet could favor histone-3 (H3) modifications, gene transcription and differentiation in the offspring neural cells even under protein-deficiency. Female rats fed a control (Ct), or 3 types of multideficient diets differing in protein levels or linoleic/alpha-linolenic fatty acid ratios (RBD, RBD-C, RBD-SO) from 30 days prior to mating and during pregnancy. Cerebral cortex tissue and cortical cultures of progeny embryonic neurons and postnatal astrocytes were analyzed. H3K9 acetylation and H3K27 or H3K4 di-methylation levels were assessed by flow cytometry and/or immunocytochemistry. In astrocyte cultures and cortical tissue, the GFAP protein levels were assessed. Glial derived neurotrophic factor (GDNF) and leukemia inhibitory factor (LIF) gene expression were evaluated in the cortical tissue. GFAP levels were similar in astrocytes of Ct, RBD and RBD-C, but 65% lower in RBD-SO group. Higher levels of H3K9Ac were found in the neurons and H3K4Me2 in the astrocytes of the RBD group. No intergroup difference in the cortical GDNF mRNA expression or the H3K27Me2 levels in astrocytes was detected. LIF mRNA levels were higher in the RDB (P=.002) or RBD-C (P=.004) groups than in the control. The findings indicate the importance of dietary n-3 availability for the brain, even under a protein-deficient condition, inducing Histone modifications and increasing LIF gene transcription, involved in neural cell differentiation and reactivity. [Display omitted]