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Experiences, Including Learning and Drug Use, Leave Genetic Marks on Brain Behavior—Neuroscience 2013

New human and animal research released today demonstrates how experiences impact genes that influence behavior and health. Today’s studies, presented at a press conference of Neuroscience 2013, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health, provide new insights into how experience might produce long-term brain changes in behaviors like drug addiction and memory formation. 30,000 scientists are attending this meeting in San Diego. Years of heroin abuse may change how genes are expressed and how the brain functions, according to new human research described today in a news conference organized by the Society of Neuroscience. The studies focus on an area of research called epigenetics, in which the environment and experiences can turn genes “on” or “off,” while keeping underlying DNA intact. These changes affect normal brain processes, such as development or memory, and abnormal brain processes, such as depression, drug dependence, and other psychiatric disease — and can be passed down to subsequent generations. According to the World Health Organization, 9.5 million people abuse heroin around the world, which increases their risk of death by 20 to 30 times compared to that of non-drug users. “Our study addresses a critical gap in our knowledge about heroin addiction because we cannot often directly study the brains of addicted humans,” said senior author Yasmin Hurd, Ph.D., of the Icahn School of Medicine at Mount Sinai in New York. “Our results provide important insights into how human brains change in response to long-term heroin use, and give us to knowledge to help treat this dangerous disease.” Dr. Hurd’s findings indicated that long-term heroin abusers show differences in small chemical modifications of their DNA and the histone proteins attached to it, compared to non-abusers. These differences could account for some of the changes in DNA/histone structures that develop during addiction, suggesting a potential biological difference driving long-term abuse versus overdose (Yasmin Hurd, abstract 257.2, see attached summary). The changes to brain function from heroin use are driven by epigenetics, which causes the structure of the DNA to become more “open” or “closed,” allowing some genes to be expressed more or less often. This changes what proteins are produced and, as a result, can change how the brain functions. To determine the epigenetic changes relating to opiate abuse, Dr. Hurd and her colleagues examined the post-mortem brains of heroin abusers, looking at which genes were being “used” to make functional molecules, and at what levels. The team focused on the striatum, an area of the brain that is closely involved in drug abuse. They found significant changes to how DNA was being “used,” and this disturbance was correlated with the number of years of heroin addiction. Strikingly, there was an inverse correlation between “open” DNA and heroin overdose, suggesting that chronic drug abuse produces different changes than those resulting from drug overdose. This indicates that the behaviors that lead to overdose have a different neural basis than those that lead to long-term abuse. In addition to Dr. Hurd’s work, other presented research included the following: male rats exposed to cocaine may pass epigenetic changes on to their male offspring, thereby altering the next generation’s response to the drug. Researchers found that male offspring in particular responded much less to the drug’s influence (Matheiu Wimmer, Ph.D., abstract 449.19); drug addiction can remodel mouse DNA and chromosomal material in predictable ways, leaving “signatures,” or signs of the remodeling, over time. A better understanding of these signatures could be used to diagnose drug addiction in humans (Eric Nestler, Ph.D., abstract 59.02); researchers have identified a potentially new genetic mechanism, called piRNA, underlying long-term memory. Molecules of piRNA were previously thought to be restricted to egg and sperm cells (Eric Kandel, M.D., co-recipient of the 2000 Nobel Prize in Physiology or Medicine); epigenetic DNA remodeling is important for forming memories. Blocking this process causes memory deficits and stunts brain cell structure, suggesting a mechanism for some types of intellectual disability (Marcelo Wood, Ph.D.). “DNA may shape who we are, but we also shape our own DNA,” said press conference moderator Schahram Akbarian, M.D., Professor of Psychiatry and Professor of Neuroscience at the Icahn School of Medicine at Mount Sinai, an expert in epigenetics. “These findings show how experiences like learning or drug exposure change the way genes are expressed, and could be incredibly important in developing treatments for addiction and for understanding processes like memory.” Neuroscience 2013 continues through Wednesday, November 13. [Neuroscience 2013 Program >] [Society for Neuroscience 2013 meeting]