Tryptophan diet deficiency, intermittent hypoxia exposure and DNA methylation: implications in SIDS (710.10)

Abstract

The Sudden Infant Death Syndrome (SIDS) is the unexpected, sudden death of an infant in which an autopsy and a death scene investigation do not find a cause of death. Here, we focus on the role of brainstem serotonin (5‐HT) deficiency in SIDS pathogenesis as suggested by studies in SIDS cases. Further, a recent discovery of the effects of neonatal chronic intermittent hypoxia (CIH), a postulated occurrence in many SIDS cases, on DNA methylation as measured in adult rats suggests a potential role of epigenetics in the pathogenesis of SIDS. The present study investigated the effects of neonatal CIH on DNA methylation in rat pups treated with control vs. tryptophan deficient diets, the latter known to induce a brainstem 5‐HT deficiency. Our data suggest that global DNA methylation in the medulla increased significantly with tryptophan deficiency (Two way ANOVA, p<0.001) whereas exposure to CIH decreased it (p<0.001). Interestingly, there was a significant interaction effect between diet and CIH (p = 0.010). Similarly, DNA methylation in the raphe increased with tryptophan deficiency whereas the addition of CIH decreased it, demonstrating a significant interaction between diet and CIH (p = 0.029). Thus we find that two different risk factors associated with SIDS can result in epigenetic modification in the brainstem. It is unclear what the role of such epigenetic modification is in the context of 5‐HT deficiency, CIH and SIDS.Grant Funding Source: Supported by National Institute of Child Health and Human Development Grant PO1‐HD‐036379