I recently listed to an podcast episode from Stuff You Should Know called, Can your Grandfather’s diet shorten your life. The podcast was about Epigenetics. Epigenetics, “is the study of inherited changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence”
In simple terms, I understand this to mean that I can change the look of my DNA without actually changing the DNA itself and that this change can be made by external (man controlled) circumstances.
“Scientists first coined the term “epigenetic” (which literally means “above the genome”) in the 1940s as a way of classifying changes that occurred between genome and phenotype. For instance, why would only one identical twin develop cancer and not both? In a quest to understand what was happening, scientists looked more closely at the relationship between DNA and cellular development.
DNA resides inside the nucleus of a cell, a master program in the center of every minute piece that makes us who we are. Enzymes attach carbon and hydrogen bundles (CH3) called methyl groups to the DNA, often near the beginning of a gene — the same place where proteins attach to activate the gene. If the protein can’t attach due to a blocking methyl group, then the gene usually remains off. Scientists call this particular epigenetic process methylation. The arrangement of these bundles can change drastically in the course of a lifetime, but also can set permanently during embryo development. It all depends on the various factors that can affect the distribution of methyl groups.”
So what does this all have to do with women who were pregnant during 9/11 and suffer from PSTD?
“…recent observations in infants born to mothers who were pregnant on 9/11 demonstrate that low cortisol in relation to parental PTSD appears to be present early in the course of development and may be influenced by in utero factors such as glucocorticoid programming. Since low cortisol levels are particularly associated with the presence of maternal PTSD the findings suggest the involvement of epigenetic mechanisms.”
This is saying that women who were pregnant on September 11th, 2001 and experienced PTSD had increased cortisol levels. These increased levels that are directly related to PTSD were seen in the development of the babies own mental well-being by effecting the DNA strand.
Here is another example, “As the saying goes, you are what you eat. Research has shown that shortages or excesses of food during a person’s childhood can cause epigenetic changes that lead to diabetes, obesity and early puberty. Adaptations that made sense during a time of famine can then transfer to children and grandchildren who live in a time of plenty. Genes become epigenetically set to deal with adverse conditions and then pass on to offspring who may enjoy comfier conditions. Experiments have also shown how foods can cause epigenetic changes in the womb. Scientists have influenced coat colors and deterred obesity in mice by feeding the mother a soy-rich diet, which alters methylation.”
I find this whole article fascinating because it really drives home to me that not only do I need to work on teaching my children good eating skills, I also need to teach them that their eating habits, choices, mental health will effect the success or failure of their children. In a way it is amazing to think that you could bring relief to things such as PTSD, Autism, and Mental Illness all my altering your diet and in turn changing your genetic look. Yet, it is also terrifying to think that my own life experiences and choices have already altered my children’s chance for success.
The following is the article in its entirety that spark my desire to learn more. I happen to read it in the doctors office while I was waiting to get my flu shot last month…
The Brain: The Switches That Can Turn Mental Illness On and Off
06.16.2010
The difference between one personality and another is not determined by genes alone. Love’s got something to do with it too. by Carl Zimmer
This month’s column is a tale of two rats. One rat got lots of attention from its mother when it was young; she licked its fur many times a day. The other rat had a different experience. Its mother hardly licked its fur at all. The two rats grew up and turned out to be very different. The neglected rat was easily startled by noises. It was reluctant to explore new places. When it experienced stress, it churned out lots of hormones. Meanwhile, the rat that had gotten more attention from its mother was not so easily startled, was more curious, and did not suffer surges of stress hormones.
The same basic tale has repeated itself hundreds of times in a number of labs. The experiences rats had when they were young altered their behavior as adults. We all intuit that this holds true for people, too, if you replace fur-licking with school, television, family troubles, and all the other experiences that children have. But there’s a major puzzle lurking underneath this seemingly obvious fact of life. Our brains develop according to a recipe encoded in our genes. Each of our brain cells contains the same set of genes we were born with and uses those genes to build proteins and other molecules throughout its life. The sequence of DNA in those genes is pretty much fixed. For experiences to produce long-term changes in how we behave, they must be somehow able to reach into our brains and alter how those genes work.
Neuroscientists are now mapping that mechanism. Our experiences don’t actually rewrite the genes in our brains, it seems, but they can do something almost as powerful. Glued to our DNA are thousands of molecules that shut some genes off and allow other genes to be active. Our experiences can physically rearrange the pattern of those switches and, in the process, change the way our brain cells work. This research has a truly exciting implication: It may be possible to rearrange that pattern ourselves and thereby relieve people of psychiatric disorders like severe anxiety and depression. In fact, scientists are already easing those symptoms in mice.
Two families of molecules perform that kind of genetic regulation. One family consists of methyl groups, molecular caps made of carbon and hydrogen. A string of methyl groups attached to a gene can prevent a cell from reading its DNA sequence. As a result, the cell can’t produce proteins or other molecules from that particular gene. The other family is made up of coiling proteins, molecules that wrap DNA into spools. By tightening the spools, these proteins can hide certain genes; by relaxing the spools, they can allow genes to become active.
Together the methyl groups and coiling proteins—what scientists call the epigenome—are essential for the brain to become a brain in the first place. An embryo starts out as a tiny clump of identical stem cells. As the cells divide, they all inherit the same genes but their epigenetic marks change. As division continues, the cells pass down not only their genes but their epigenetic marks on those genes. Each cell’s particular combination of active and silent genes helps determine what kind of tissue it will give rise to—liver, heart, brain, and so on. Epigenetic marks are remarkably durable, which is why you don’t wake up to find that your brain has started to turn into a pancreas.
Our experiences can rewrite the epigenetic code, however, and these experiences can start even before we’re born. In order to lay down the proper pattern of epigenetic marks, for example, embryos need to get the raw ingredients from their mothers. One crucial ingredient is a nutrient called folate, found in many foods. If mothers don’t get enough folate, their unborn children may lay down an impaired pattern of epigenetic marks that causes their genes to malfunction. These mistaken marks might lead to spina bifida, a disease in which the spinal column fails to form completely.
Other chemicals can interfere with epigenetic marks in embryos. Last year, Feng C. Zhou of Indiana University found that when pregnant lab rats consumed a lot of alcohol, the epigenetic marks on their embryos changed dramatically. As a result, genes in their brains switched on and off in an abnormal pattern. Zhou suspects that this rewriting of the epigenetic code is what causes the devastating symptoms of fetal alcohol syndrome, which is associated with low IQ and behavioral problems.
Even after birth the epigenetic marks in the brain can change. Over the past decade, Michael Meaney, a neurobiologist at McGill University, and his colleagues have been producing one of the most detailed studies of how experience can reprogram the brain’s genes. They are discovering the molecular basis for the tale of the two rats.
The differences between rats that got licked a lot and those that got licked only a little do not emerge from differences in their genes. Meaney found that out in an experiment involving newborn rat pups. He took pups whose mothers who didn’t lick much and placed them with foster mothers who licked a lot, and vice versa. The pups’ experience with their foster mothers—not the genes they inherited from their biological mothers—determined their personality as adults.
To figure out how licking had altered the rats, Meaney and his colleagues looked closely at the animals’ brains. They discovered major differences in the rats’ hippocampus, a part of the brain that helps organize memories. Neurons in the hippocampus regulate the response to stress hormones by making special receptors. When the receptors grab a hormone, the neurons respond by pumping out proteins that trigger a cascade of reactions. These reactions ripple through the brain and reach the adrenal glands, putting a brake on the production of stress hormones.
In order to make the hormone receptors, though, the hippocampus must first receive signals. Those signals switch on a series of genes, which finally cause neurons in the hippocampus to build the receptors. Meaney and his colleagues discovered something unusual in one of these genes, known as the glucocorticoid receptor gene: The stretch of DNA that serves as the switch for this gene was different in the rats that got a lot of licks, compared with the ones that did not. In the rats without much licking, the switch for the glucocorticoid receptor gene was capped by methyl groups, and the neurons in the underlicked rats did not produce as many receptors. The hippocampus neurons therefore were less sensitive to stress hormones and were less able to tamp down the animal’s stress response. As a result, the underlicked rats were permanently stressed out.
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These studies hint at how experiences in youth can rewrite the epigenetic marks in our brains, altering our behavior as adults. Meaney and his colleagues cannot test this hypothesis by running similar experiments on humans, of course, but last year they published a study that came pretty close.
Meaney’s team examined 36 human brains taken from cadavers. Twelve of the brains came from people who had committed suicide and had a history of abuse as children. Another 12 had committed suicide without any such history. The final 12 had died of natural causes. The scientists zeroed in on the cells from the hippocampi of the cadavers, examining the switch for the stress hormone gene they had studied in rats. Meaney and his colleagues found that the brains of people who had experienced child abuse had relatively more methyl groups capping the switch, just as the researchers had seen in rats that had not been licked much as pups. And just as those rats produced fewer receptors for stress hormones, the neurons of the people who had suffered child abuse had fewer receptors as well.
Child abuse may leave a mark on its victims in much the same way that parental neglect affects rat pups. Abuse seems to have altered the epigenetic marks in their hippocampi. As a result, they made fewer stress receptors on their neurons, which left them unable to regulate their stress hormones, leading to a life of anxiety. That extra stress may have played a part in their committing suicide.
The hippocampus is probably not the only place where experiences rewrite epigenetic marks in the brain. An international group of researchers recently compared the brains of 44 people who had committed suicide with those of 33 people who died of natural causes. The scientists looked at a gene that produces the protein BDNF, which promotes hormone receptors, in a part of the brain called the Wernicke area. That area, located behind the left ear in most people, helps us interpret the meanings of words. In March the researchers reported that the BDNF switch had more methyl groups attached to it in the Wernicke area of suicide victims than in other people.
And the influence of environment doesn’t end with childhood. Recent work indicates that adult experiences can also rearrange epigenetic marks in the brain and thereby change our behavior. Depression, for example, may be in many ways an epigenetic disease. Several groups of scientists have mimicked human depression in mice by pitting the animals against each other. If a mouse loses a series of fights against dominant rivals, its personality shifts. It shies away from contact with other mice and moves around less. When the mice are given access to a machine that lets them administer cocaine to themselves, the defeated mice take more of it.
Eric Nestler, a neuroscientist at Mount Sinai School of Medicine in New York City, wondered what the brains of these depressed mice looked like. Last fall he reported discovering an important difference in a region of the brain called the nucleus accumbens. It was probably no coincidence that depression altered this region, since the nucleus accumbens plays an important role in the brain’s reward system, helping to set the value we put on things and the pleasure we get from them.
The change Nestler and his colleagues discovered in the nucleus accumbens was epigenetic: Some of the DNA in the neurons in that region became more tightly or less tightly wound in depressed mice. Such an epigenetic change might permanently alter which genes are active in the brains of those mice. The same may hold true for humans. Nestler’s team looked at cadaver brains from people who had been diagnosed with depression in life. They discovered the same epigenetic changes in the human nucleus accumbens.
If scientists can pinpoint the epigenetic changes that our experiences impart, it may be possible to reverse those changes. Nestler and his colleagues pumped drugs known as HDAC inhibitors into the nucleus accumbens of their depressed mice. These drugs can loosen tight spools of DNA, making it possible for cells to gain access to genes again. Ten days after treatment, the mice were more willing to approach other mice. The drug also erased many other symptoms of depression in the animals.
The possibility that we can rewrite the epigenetic code in our brains may be exciting, but it is also daunting. Modifying epigenetic markers is not easy—and that’s a good thing. After all, if our methyl groups and coiling proteins were constantly shifting, depression would be the least of our problems. Nothing ruins your day like finding that your brain has turned into a pancreas.
Links
- HHMI Online Companion
www.hhmi.org/resources/science_now/epigenetics.html
The Howard Hughes Medical Institute provides an extensive collection of resources on epigenetics in its online companion to this segment of NOVA scienceNOW. - Human Epigenome Project
www.epigenome.org
Learn about current epigenetics research on this Web site from the Human Epigenome Project. - Epigenetics?
epigenome.eu
This comprehensive site offers news, articles, and other resources on the study of epigenetics. - Jirtle Lab at Duke University
www.geneimprint.com/lab/
On the homepage of Randy Jirtle’s laboratory at Duke University, browse epigenetics-related articles, learn about current research projects, read recent academic publications, and more. - Epigenetics
www.landesbioscience.com/journals/epigenetics
The official journal of the Epigenetics Society offers downloadable academic papers addressing new research in the field. Some articles require subscription. - Human Epigenome Project—Up and Running
www.pubmedcentral.nih.gov/articlerender.fcgi?artid=300691
On this Web site from the National Institutes of Health, learn about how methyl groups alter genetic expression and discover some of the practical applications of epigenetic research.
Articles
“Epigenetics: The Science of Change”
by Bob Weinhold. Environmental Health Perspectives, March 2006.
www.ehponline.org/members/2006/114-3/focus.html
Books
- Epigenetics
edited by C. David Allis, Thomas Jenuwein, Danny Reinberg, and Marie-Laure Caparros. Cold Spring Harbor Laboratory Press, 2006. - Chromatin and Gene Regulation: Mechanisms in Epigenetics
by Bryan Turner. Blackwell Publishing, 2002.
Foot Notes:
1 Epigenetics. (n.d.). Wikipedia, the free encyclopedia. Retrieved October 08, 2010, from http://en.wikipedia.org/wiki/Epigenetics
2 Lamb, Robert. “How Epigenetics Works” 13 October 2008. HowStuffWorks.com. <http://science.howstuffworks.com/environmental/life/genetic/epigenetics.htm> 08 October 2010.
3 The Traumatic Stress Studies Program, Department of Psychiatry, Mount Sinai School of Medicine and Bronx Veterans Affairs, James J. Peters VAMC, 116-A, OOMH-PTSD, 130 West Kingsbridge Road, Bronx, NY 10468, USA
4 Lamb, Robert. “How Epigenetics Works” 13 October 2008. HowStuffWorks.com. <http://science.howstuffworks.com/environmental/life/genetic/epigenetics.htm> 08 October 2010.
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