By Jeaneane Swanson
In biology class, most of us were taught to believe that specific traits are passed on through our genes: if I have the “Alzheimer’s gene” or the “breast cancer gene,” there’s a probable chance that my son or daughter will carry that gene. However, what about more “complex” diseases like depression, or alcoholism? While alcoholism does tend to run in families—and has a genetic component—how exactly is it passed on?
In recent years, more and more studies are showing that there is another level of inheritance at work: epigenetics. Literally “above the genome,” epigenetic marks are chemical “tags” that can be put on or taken off DNA, and their purpose is to control the expression of genes. Some tags turn genes on, while others turn genes off. These tags come in the form of molecules called methyl groups or acetyl groups, and they can also appear on the outside of the DNA strand. In the nucleus of every cell, the very long strands of DNA coil around proteins called histones; these histones can be more “open” or “closed,” depending on what tags reside on the surface.
These “tags” can be helpful and are very important for many biological processes. For example, in the development of an embryo into a baby, epigenetics plays a huge role in making sure embryonic cells differentiate at the right time and place. Ever wonder how a small handful of cells become heart and lung and brain cells, and all the other cells in our bodies? Since every single cell contains all of our DNA, some genes have to be turned off, while others left on, in order for there to be different types of cells.
However, the epigenome is ever changing; marks can come, and marks can go. In fact, the epigenome is highly sensitive to the environment. Environmental Factors such as diet, stress, and exposure to environmental toxins can alter the arrangement of these tags and cause disease. And, it’s being increasingly shown, disease in not just us, but in our kids, and our grandkids. Groundbreaking—and controversial—studies by epigenetics researcher Michael Skinner at Washington State University have not only brought to the forefront the idea of endocrine disruptors, but that these environmentally harmful chemicals can leave marks on the genome that can be passed on through germ cells—sperm and egg—to next generations. This new field has become known as transgenerational epigenetic inheritance.
And while there are examples of traits that have been inherited across multiple generations in everything from seeds to rodents to humans—DNA methylation patterns in response to environmental toxins, for instance—“no one has looked in terms of drugs of abuse,” says Ghazaleh Sadri-Vakili, an assistant professor at Harvard Medical School and the director of the neuroepigenetics laboratory of the MassGeneral Institute for Neurodegenerative Disease. That is, until now.
Building off this previous work, several recent studies in rodents have, indeed, delved into how drug and alcohol use affects the epigenome of the offspring. While mothers can harm the baby in utero, as well as subject it to stress and abuse as a child, researchers are beginning to ask the question: Can the effects of parents’ substance abuse be felt by their children, even if they stopped using years before?
These new findings suggest that if a parent uses drugs, he or she could pass on that DNA “damage” in the form of inherited epigenetic changes. What’s more, these epigenetic changes can predispose the offspring to not only becoming addicts, but to having to grapple with the behavioral traits that make it so hard to resist the pull of using, like impulsivity and heightened sensitivity to drugs.
THE EPIGENETICS OF ADDICTION
The hallmarks of addiction are tolerance and then, sensitization. Sensitization happens when a user becomes overly sensitive to a drug’s high or rewarding effect; accompanied by intense cravings and often, relapse. Eric Nestler, a leading figure in studying the epigenetic changes associated with addiction, discovered two key transcription factors that remain turned on after using drugs, thereby leading to symptoms of tolerance. (A transcription factor is a protein that parks itself next to a gene and turns it on.)
However, what was keeping the transcription factors around, they themselves being proteins from active genes? “The heightened sensitivity, it turns out, stems from epigenetic modifications of the genes,” Nestler, who is the director of the Friedman Brain Institute at the Mount Sinai School of Medicine, wrote in an article for Scientific American magazine in 2011.
In recent years, Nestler’s lab has conducted a series of studies on rodents that show how cocaine use can affect the genetic activity in certain parts of the brain. In one, he found that chronic cocaine use changes the pattern of acetyl and methyl tags on hundreds of genes within the brain’s reward center; and these changes make these genes more active when subsequently exposed to cocaine. In another paper, they found that chronic cocaine administration dials down the activity of certain molecules that remove acetyl groups, and of certain molecules that add methyl groups—in both cases making the genes more active with more cocaine. Epigenetic modifications have been observed in rats that use alcohol, nicotine, cocaine, amphetamines, and opiates.
Many of these changes are transient, lasting only a few hours after the animal receives the drug. Some last much longer, however; Nestler’s group has seen changes last as long as a month, and they’re looking into even longer times. In fact, if Skinner and others are right, it’s the very long-lasting nature of these epigenetic changes that make them heritable.