DNA Methylation Profiles of Selected Pro-Inflammatory Cytokines in Alzheimer Disease

Abstract

By means of functional genomics analysis, we recently described the mRNA expression profiles of various genes involved in the neuroinflammatory response in the brains of subjects with late-onset Alzheimer Disease (LOAD). Some of these genes, namely interleukin (IL)-1β and IL-6, showed distinct expression profiles with peak expression during the first stages of the disease and control-like levels at later stages. IL-1β and IL-6 genes are modulated by DNA methylation in different chronic and degenerative diseases; it is also well known that LOAD may have an epigenetic basis. Indeed, we and others have previously reported gene-specific DNA methylation alterations in LOAD and in related animal models. Based on these data, we studied the DNA methylation profiles, at single cytosine resolution, of IL-1β and IL-6 5'-flanking region by bisulphite modification in the cortex of healthy controls and LOAD patients at 2 different disease stages: Braak I-II/A and Braak V-VI/C. Our analysis provides evidence that neuroinflammation in LOAD is associated with (and possibly mediated by) epigenetic modifications.

CpG and Non-CpG Methylation in Epigenetic Gene Regulation and Brain Function

“…Thus, epigenetic alterations in the mammalian brain result in impairment of brain development and neurodevelopmental disorders [95,96,97]. Recent studies have raised concern regarding the effects of aberrant DNA methylation on the origin and progression of neurodegenerative disorders.…”

“…Gene-specific DNA methylation alterations are thought to be related to AD and AD animal models [97]. AD is characterized by progressive deficits in cognition and memory caused by neuronal degeneration and neuron loss.…”

“…Only IL-1β had a pattern of DNA methylation that correlated with gene expression levels. It was little correlation between DNA methylation and gene expression levels for IL-6 and C3ar1 [97]. Thus, it may be possible that other epigenetic modifications are more important in controlling AD-related genes.…”

Potential neurotoxicity of prenatal exposure to sevoflurane on offspring: Metabolomics investigation on neurodevelopment and underlying mechanism

“…2, indicating that sevoflurane might induce abnormal methylation in offspring. Abnormal methylation leads to many diseases, including neuroinflammation (Nicolia et al, 2017). In this study, presence of leukotriene E4 might hint that prenatal exposure to sevoflurane caused neuroinflammation in offspring.…”

“…In this study, presence of leukotriene E4 might hint that prenatal exposure to sevoflurane caused neuroinflammation in offspring. Meanwhile, since inflammatory genes were regulated by methylation in neurodegenerative diseases (Nicolia et al, 2017), it was plausible that methylation served as a crucial role between neuroinflammation and neurotoxicity, and this assumption has been partially confirmed (Zhu et al, 2017).…”