Abstract
BackgroundDNA 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.ResultsBy 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, P = 0.033).ConclusionsOur 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.
Highlights
DNA methylation has been viewed as the most highly characterized epigenetic mark for genome regulation and development
[1,2,3, 10], our study provides a striking view of how the epigenetic DNA methylation landscape of the thalamus and the hippocampus in postnatal individuals is modified in response to malnourishment
Discriminable variations related to neuronal development and psychiatric disorders were observed in the thalamus
Summary
DNA methylation has been viewed as the most highly characterized epigenetic mark for genome regulation and development. The purpose of this study was to examine how extensively the brain DNA methylome is regulated by nutrition in early life. Nutrition represents one of the major important variables that play crucial roles in the maturation and functional development of the central nervous system (CNS) [1]. Growth deficits due to malnutrition in childhood increase the incidence of infectious diseases and lead to alterations in CNS function, which have been shown to delay psychomotor development [3]. DNA methylation is among the best studied epigenetic modifications and is essential to mammalian development [4]. Many epigenetic studies on DNA methylation have revealed that malnutrition during the perinatal period is highly correlated with abnormal neurodevelopment [6]
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