Formaldehyde playing a role in (de)methylation for memory

Abstract

Methylation of DNA, RNA, and histone is one of the mechanisms for epigenetic regulation that occurs by the addition of a methyl (CH3) group to DNA, RNA, and histone, thereby often modifies the function of the genes through chromatin remodeling. As described by recent studies, methylation of DNA or histone is regarded as a critical step in the process of memory formation. Formaldehyde as a methyl donor for the methylation of DNA, RNA, and histone acts as an epigenetic factor participating in the reversible and dynamic methylation. DNA demethylation elicits formaldehyde generation in the dividing cells and post-mitotic neurons. Endogenous formaldehyde is observably increased in aging population, but DNA methylation decreases, which closely links learning-responsive DNA methylation and memory formation. Dysmetabolism of endogenous formaldehyde, which affects DNA and histone methylation, is involved in age-related cognitive impairment. The level of formaldehyde is positively correlated with cognitive impairment, such as Alzheimer's disease (AD) and post-stroke dementia (PSD). Enhancement of DNA demethylation or block of DNA re-methylation using 5-aza-2-deoxycytidine (an inhibitor of DNA methyltransferase, DNMT) in rats leads to spatial memory deficits during spatial memory formation. Scavenging the elevated formaldehyde effectively relieves memory loss for rats. Here, we discuss the role of endogenous formaldehyde in methylation and demethylation of DNA, RNA, and histone as well as the formation or loss of memory.