Author(s)

Hao Zhu, Yijing Ding, Weimin Zhu, Shuang Liang, Yanyan Qian, Yuanpeng Zhou, Duan Ma, Huijun Wang, Weidong Tian, Shufeng Zhou, Xiaotian Li

Institute of Biomedical Sciences, Fudan University, Shanghai, China.
Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
School of Life Science, Institute of Biostatistics, Fudan University, Shanghai, China.
School of Pharmacy, University of South Florida, Tampa, USA.

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.

Maternal Protein Malnutrition, Morris Water Maze, Methylation, Grin2b, NMDA Receptors

Zhu, H. , Ding, Y. , Zhu, W. , Liang, S. , Qian, Y. , Zhou, Y. , Ma, D. , Wang, H. , Tian, W. , Zhou, S. and Li, X. (2014) Long-Term Impact of Maternal Protein Malnutrition on Learning and Memory Abilities and DNA Methylating Profiles of the Nervous System in Offspring Rats. Health, 6, 2047-2065. doi: 10.4236/health.2014.615239.