DNA methylation is unlikely to influence the production of the protein that detects acetophenone, he says. However, Timothy Bestor, a molecular biologist at Columbia University in New York who studies epigenetic modifications, is incredulous. David Sweatt, a neurobiologist at the University of Alabama at Birmingham who was not involved in the work, calls it “the most rigorous and convincing set of studies published to date demonstrating acquired transgenerational epigenetic effects in a laboratory model". “The overwhelming response has been 'Wow! But how the hell is it happening?'" says Dias. Predictably, the study has divided researchers. Ressler notes that sperm cells themselves express odorant receptor proteins, and that some odorants find their way into the bloodstream, offering a potential mechanism, as do small, blood-borne fragments of RNA known as microRNAs, that control gene expression. In the fearful mice, the acetophenone-sensing gene of sperm cells had fewer methylation marks, which could have led to greater expression of the odorant-receptor gene during development.īut how the association of smell with pain influences sperm remains a mystery. ![]() The researchers propose that DNA methylation - a reversible chemical modification to DNA that typically blocks transcription of a gene without altering its sequence - explains the inherited effect. Structures that receive signals from the acetophenone-detecting neurons and send smell signals to other parts of the brain (such as those involved in processing fear) were also bigger. The mice sensitized to acetophenone, as well as their descendants, had more neurons that produce a receptor protein known to detect the odour compared with control mice and their progeny. These responses were paired with changes to the brain structures that process odours. Similar experiments showed that the response can also be transmitted down from the mother. A third generation of mice - the 'grandchildren' - also inherited this reaction, as did mice conceived through in vitro fertilization with sperm from males sensitized to acetophenone. Despite never having encountered acetophenone in their lives, the offspring exhibited increased sensitivity when introduced to its smell, shuddering more markedly in its presence compared with the descendants of mice that had been conditioned to be startled by a different smell or that had gone through no such conditioning. This reaction was passed on to their pups, Dias and Ressler report today in Nature Neuroscience1. The animals eventually learned to associate the scent with pain, shuddering in the presence of acetophenone even without a shock. He and Dias wafted the scent around a small chamber, while giving small electric shocks to male mice. So Ressler and his colleague Brian Dias opted to study epigenetic inheritance in laboratory mice trained to fear the smell of acetophenone, a chemical the scent of which has been compared to those of cherries and almonds. Studying the biological basis for those effects in humans would be difficult. “There are a lot of anecdotes to suggest that there’s intergenerational transfer of risk, and that it’s hard to break that cycle,” he says. Kerry Ressler, a neurobiologist and psychiatrist at Emory University in Atlanta, Georgia, and a co-author of the latest study, became interested in epigenetic inheritance after working with poor people living in inner cities, where cycles of drug addiction, neuropsychiatric illness and other problems often seem to recur in parents and their children. Yet although epigenetic modifications are known to be important for processes such as development and the inactivation of one copy of the X-chromsome in females, their role in the inheritance of behaviour is still controversial. ![]() ![]() For instance, children who were conceived during a harsh wartime famine in the Netherlands in the 1940s are at increased risk of diabetes, heart disease and other conditions - possibly because of epigenetic alterations to genes involved in these diseases. Yet some studies have hinted that environmental factors can influence biology more rapidly through 'epigenetic' modifications, which alter the expression of genes, but not their actual nucleotide sequence. Random DNA mutations, when beneficial, enable organisms to adapt to changing conditions, but this process typically occurs slowly over many generations. But some researchers are sceptical of the findings because a biological mechanism that explains the phenomenon has not been identified.Īccording to convention, the genetic sequences contained in DNA are the only way to transmit biological information across generations. The authors suggest that a similar phenomenon could influence anxiety and addiction in humans. Certain fears can be inherited through the generations, a provocative study of mice reports.
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