Aging-associated excess formaldehyde leads to spatial memory deficits

作者：Zhiqian Tong, Chanshuai Han, Wenhong Luo, Hui Li, Hongjun Luo, Min Qiang, Tao Su, Beibei Wu, Ying Liu, Xu Yang, You Wan, Dehua Cui, Rongqiao He · 发表于：Scientific Reports · 年份：2013 · DOI：10.1038/srep01807 · 被引用次数：112 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Epigenetics and DNA Methylation、Genomics, phytochemicals, and oxidative stress

Recent studies show that formaldehyde participates in DNA demethylation/methylation cycle. Emerging evidence identifies that neuronal activity induces global DNA demethylation and re-methylation; and DNA methylation is a critical step for memory formation. These data suggest that endogenous formaldehyde may intrinsically link learning-responsive DNA methylation status and memory formation. Here, we report that during spatial memory formation process, spatial training induces an initial global DNA demethylation and subsequent re-methylation associated with hippocampal formaldehyde elevation then decline to baseline level in Sprague Dawley rats. Scavenging this elevated formaldehyde by formaldehyde-degrading enzyme (FDH), or enhancing DNA demethylation by a DNA demethylating agent, both led to spatial memory deficits by blocking DNA re-methylation in rats. Furthermore, we found that the normal adult rats intrahippocampally injected with excess formaldehyde can imitate the aged-related spatial memory deficits and global DNA methylation decline. These findings indicate that aging-associated excess formaldheyde contributes to cognitive decline during aging.