On August 21, 2017, there was a total solar eclipse–the first one in my quarter century on earth–and I missed it. While it is true that it would have only been a partial solar eclipse where I live, there is something distressing about missing out on a major public event that all your friends and family are participating in across the United States.
On the other hand, I was in Italy participating in a one week intensive course on neuroepigenetics (which, the nerd that I am, was very exciting as well).
If “neuroepigenetics” is a word you have never heard before, then you are not alone. My spell check doesn’t even know this word, so I thought I would take this opportunity to write about the history and concepts that I learned about this last week (this post goes out to my parents, who keep asking what it is that I do). It’s going to be a little technical, so bear with me and message me if there are topics I need to go more in depth with.
What is “Neuroepigenetics?”
First, we have the concept of “epigenetics.” This was defined as a stable and heritable set of changes to our genetic phenotype without changing the actual genotype. Basically, how our environment can change our genetic expression without changing our DNA sequence that can then be inherited by our children. Let’s unpack this a little further with an analogy or two:
If you give a musical conductor nothing but notes (in this case the notes would be the DNA) with no indication of when or how to play those notes, the music played as-is wouldn’t sound very pretty–assuming the conductor could make any sense of the composition at all. Epigenetics is the annotations on the music telling someone how to play it (time signature, cleft, tempo, whether notes are half or quarter notes, etc.).
If that was too far from genetics, you can think of the epigenome as the stickie notes stuck to the DNA to tell it which parts are important to express and which are not in each cell.
But what about “neuroepigenetics?” This is a newer term coined in the past fifteen years to broaden the rigid classical ideas in epigenetics to include other mechanisms and also the to loosen the description to “partially stable, sometimes heritable” changes in phenotype without changing the genotype. This gives us as researchers more wiggle room to not prove that three generations out our phenotype stands, because oftentimes it does not but the change is still persistent throughout one lifetime, or two, and these intergenerational changes are still interesting and important.
How Neuroepigenetics Works (Briefly)
There are many different ways in which our environment can modify our genes. I will write more in depth posts on each of these later on, but I wanted to give a brief explanation of the concepts involved.
First, we need to talk about how DNA is packaged into the nucleus of the cell. DNA winds itself around octamers (sets of 8) of things called histone proteins. These further condense together to create chromatin, which is dense enough to fit into the nucleus of every cell.
There are these things called “histone tails” (labeled in the image depicting DNA packaging) that can be modified by different acetyl and methyl (and other) groups. The idea behind these histone modifications is to either loosen up the DNA around the histone to make it accessible for gene transcription, or to close it up around the DNA so it cannot be accessed for gene transcription. These additions can either suppress gene expression or enhance gene expression, depending on how many methyl/acetyl/other groups are added and at which parts of the histone tail of a specific histone variant. For example, three methyl groups added to the fourth amino acid (a Lysine) of the H3 histone variant is often associated with increased gene expression, whereas two methyl groups added to the ninth amino acid (also a Lysine–these are often what is acetylated or methylated) of the H3 histone variant is often associated with decreased gene expression.
Methyl groups can also be added to the DNA itself to “silence” that part of the DNA.
Also the chromatin itself can be remodeled by other molecules that can affect things.
If that seemed complicated, you and I are in the same boat. After a week of hearing from experts in neuroepigenetics, I’m overwhelmed with the types of modifications and the amount of histone variants and the immense quantity of things I don’t know yet.
All of these individual mechanisms and their integrations are pretty cool if you’re a nerd like me, but why does anyone else have to think about it? Well, I’m glad you asked.
When we think about, say, memory problems as we all get older (which is going to happen regardless of whether someone has dementia or not), we may think it is something that is just built into our genetics and that there is nothing we can do about it. Well, if Dr. Marcelo Wood, one of the professors that lectured at this neuroepigenetics course I just returned from, has anything to say about it, it’s that epigenetics are also at play.
I will do a further blog post on the study itself, but in essence Dr. Wood’s lab noticed that there was hypoacetylation (not enough acetyl groups added) of histones in the hippocampus (an area associated with memory formation) in aged rats. Well, if they inhibited the molecules that de-acetylate (take away acetyl groups) histones in the hippocampus, these rats had much better memory than other aged rats that received no treatment. While there is no human treatment for something like this yet, it has major implications in both aging and intellectual disability populations.
I have given only one of many, many examples of topics that are being studied with neuroepigenetics. Dr. Farah Lubin told us about not only learning and memory, but also epilepsy. Dr. Art Petronis discussed epigenetic mechanisms that may be contributing to the risk and development of schizophrenia. I’m personally planning on looking into the neuroepigenetics underlying opiate addiction. The function prospects are pretty interesting, and I hope that the immense amount of the field that is unknown means job security rather than a dead end.
If any of this confused you, do not despair. I have plans to do more in depth posts on different aspects of neuroepigenetics. If there are specifics you want to know more about, let me know and I can focus in on those!