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Open Access Highly Accessed Research article

DNA methylation profiling in the thalamus and hippocampus of postnatal malnourished mice, including effects related to long-term potentiation

Xiaoling Weng1, Daizhan Zhou2, Fatao Liu3, Hong Zhang1, Junyi Ye1, Zhou Zhang2, Di Zhang2, Yinan Wang2, Liming Tao3, Lan Cao1, Mengyuan Kan3, Ting Wang3, Guoyin Feng23, Xiaolan Qin2, Jihui Sun4, Lin He1236* and Yun Liu15*

Author Affiliations

1 Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, PR China

2 Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai 200030, PR China

3 Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China

4 Luwan Branch of Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200030, PR China

5 Key Laboratory of Molecular Medicine, The Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, 303 Ming Dao Building, 138 Yi Xue Yuan Road, Shanghai 200032, PR China

6 Bio-X Institute, Shanghai Jiao Tong University, Small White House, 1954 Hua Shan Road, Shanghai 200030, PR China

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BMC Neuroscience 2014, 15:31  doi:10.1186/1471-2202-15-31

Published: 20 February 2014

Abstract

Background

DNA methylation has been viewed as the most highly characterized epigenetic mark for genome regulation and development. Postnatal brains appear to exhibit stimulus-induced methylation changes because of factors such as environment, lifestyle, and diet (nutrition). The purpose of this study was to examine how extensively the brain DNA methylome is regulated by nutrition in early life.

Results

By quantifying the total amount of 5-methylcytosine (5mC) in the thalamus and the hippocampus of postnatal malnourished mice and normal mice, we found the two regions showed differences in global DNA methylation status. The methylation level in the thalamus was much higher than that in the hippocampus. Then, we used a next-generation sequencing (NGS)-based method (MSCC) to detect the whole genome methylation of the two regions in malnourished mice and normal mice. Notably, we found that in the thalamus, 500 discriminable variations existed and that approximately 60% were related to neuronal development or psychiatric diseases. Pathway analyses of the corresponding genes highlighted changes for 9 genes related to long-term potentiation (5.3-fold enrichment, Pā€‰=ā€‰0.033).

Conclusions

Our findings may help to indicate the genome-wide DNA methylation status of different brain regions and the effects of malnutrition on brain DNA methylation. The results also indicate that postnatal malnutrition may increase the risk of psychiatric disorders.

Keywords:
Malnutrition; Thalamus; Hippocampus; Mouse model; Global DNA methylation status; Whole genome methylation sequencing; Long-term potentiation; Psychiatric disorders