Long-Term Impact of Maternal Protein Malnutrition on Learning and Memory Abilities and DNA Methylating Profiles of the Nervous System in Offspring Rats

Objective: To determine the mechanisms by which protein deficiency during pregnancy can lead to long-term alterations in learning and memory abilities of the offspring in rats. Study design: Fourty-two pregnant rats were fed control (n = 23) or low protein (n = 19) diets ad libitum until parturition. On the 8th week of post-natal life which represented early adulthood, eighty-four offsprings (control group: n = 52, LP group: n = 32) were determined their learning & memory ability by using the Morris water maze test. Six offprings’ brain tissue (control group: n = 3, LP group: n = 3) was also analysed for DNA methylating profiles, the GO and KEGG pathways, methylation status and twelve for protein expression (control group: n = 6, LP group: n = 6). Results: The offsprings of the protein-deficient-diet fed rats learnt faster initially then lagged behind those of the control rats, especially in female rats (p = 0.035). There were a series of genes methylated in the CpG island and pormoter area. Quantitative Mass Array data showed methylation differences in Grin2b and Grin2b_3CpG 3, 4, & 5 might be the target sites as shown by dual-luciferase assay. A decreased level of protein expression of NMDAR2B was observed. Conclusion: Differential methylation status in Grin2b and changes in expression of NMDAR2B may partially explain the long-term impact of maternal protein deficiency on the cognitive and learning capabilities of offsprings.