Epigenetics in the brain: Evidence of methylation beyond cell division

Methylation is not a gasoline additive process or nor does it have anything to do with amphetamines. I mention this because methylation is proving to be significant. It is something that happens to your DNA and despite not being very well known by the public, research is showing it to be far more important than was suspected even a few years ago. I want to mention an example of that research from neuroscience that sheds some light on that importance.

First a little background: As a simple description, methylation is a switch mechanism for DNA. Chemically, methylation of DNA takes place when a methyl group (a molecule of carbon and hydrogen, CH3) is added to either cytosine or adenine (two of the bases of DNA). The addition of a methyl group disables (turns off) the corresponding gene, that is, the gene is no longer available to guide the production of protein. Removing the methyl group, demethylation, reverses the process (turns it on). Methylation or demethylation is used within the genome to set up a pattern of active and inactive genes so that, among other things, cells become specialized. For example, a particular methylation pattern directs a cell to become a heart muscle. That pattern in then passed on (inherited) through subsequent cell divisions. The overall process is called epigenetic regulation and is one of if not the principle means of determining cell development, as in a stem cell that becomes a heart cell and stays that way through the life of an organism. It is also used to modify cell functioning in response to environmental conditions. As a rule, changes in epigenetic regulation are not inheritable through the egg or sperm (intergenerational), although the number of known exceptions is growing. The discovery and study of methylation and epigenetics is not much more than thirty years old with the bulk of the research starting in the 1990’s – it is a very young field.

Recent research in methylation continues to expand its reach. Neuroscientists primarily at the Johns Hopkins Brain Science Institute and led by Hongiun Song have been working on the role of methylation in the genome of brain cells (neurons). In previous research they had discovered that the brain cells of mice could be induced to faster growth through electric shock, which was decreasing the amount of DNA methylation. In the recent work, published in Nature Neuroscience [28 August 2011, paywalled, Neuronal activity modifies the DNA methylation landscape in the adult brain] they sequenced the genome of electrically stimulated and non-stimulated mouse brains and compared the results. They found that stimulated brains decreased or increased methylation (cytosine methylation) by 1.4%.

More significantly, they discovered that demethylation was taking place in neurons that were non-dividing on a large scale. This was surprising, as existing scientific consensus held that non-dividing cells were basically passive and the methylation would change very little, if at all. In other words, methylation in brain cells was almost exclusively for directing cell development.

“It was mind-boggling to see that so many methylation sites — thousands of sites — had changed in status as a result of brain activity,” Song says. “We used to think that the brain’s epigenetic DNA methylation landscape was as stable as mountains and more recently realized that maybe it was a bit more subject to change, perhaps like trees occasionally bent in a storm. But now we show it is most of all like a river that reacts to storms of activity by moving and changing fast.”

[Source: Johns Hopkins Medical Center]

Dr. Song’s expression is rather poetic, but the impact of this finding could be far-reaching. It implies that the methylation process in neurons has a function other than cell development (via cell division). What that function is and how exactly it works remains high on the research agenda. Since it is known that in other circumstances methylation is a means of responding to the environment, it is possible that a similar process is at work in the brain. I should mention that other studies have already forwarded the idea that methylation, or some form of epigenetics, may be the basis of memory.

Research Spectrum

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