期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：10
DOI：10.1073/pnas.2119891119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Dynamic epigenetic activity is a fundamental mechanism underpinning how the brain changes its function during development and aging and in response to environmental and disease stimuli. We developed a technology called epigenetic MRI (eMRI) that enables noninvasive imaging of DNA methylation in the brain, a major epigenetic mechanism. eMRI reveals strong regional differences in global DNA methylation in pig brains, a model with stronger resemblance to human brains than are rodents. Given the noninvasive nature of eMRI, our results pave the way for a DNA-methylation imaging paradigm for living human brains. We expect eMRI to enable many studies to unravel the molecular control of brain function and disease.
Both neuronal and genetic mechanisms regulate brain function. While there are excellent methods to study neuronal activity in vivo, there are no nondestructive methods to measure global gene expression in living brains. Here, we present a method, epigenetic MRI (eMRI), that overcomes this limitation via direct imaging of DNA methylation, a major gene-expression regulator. eMRI exploits the methionine metabolic pathways for DNA methylation to label genomic DNA through
13C-enriched diets. A
13C magnetic resonance spectroscopic imaging method then maps the spatial distribution of labeled DNA. We validated eMRI using pigs, whose brains have stronger similarity to humans in volume and anatomy than rodents, and confirmed efficient
13C-labeling of brain DNA. We also discovered strong regional differences in global DNA methylation. Just as functional MRI measurements of regional neuronal activity have had a transformational effect on neuroscience, we expect that the eMRI signal, both as a measure of regional epigenetic activity and as a possible surrogate for regional gene expression, will enable many new investigations of human brain function, behavior, and disease.
