Painful memories such as child abuse or those resulting from wartime service can leave markers on DNA in the brain, making it difficult to remove these memories with common behavioral therapies. Recent studies at the Massachusetts Institute of Technology in Cambridge (MIT) have resulted in the discovery of a drug with the ability to remove these markers from DNA increasing the effectiveness of behavioral treatments in conditions such as PTSD. Research on mice has demonstrated that these epigenetic markers can be removed allowing the brain to dissociate a specific memory from the emotion it is linked with.
According to the MIT researchers, in individuals with anxiety disorders such as Post-Traumatic Stress Disorder (PTSD), a specific traumatic memory doesn’t go away with time as it would normally. According to Li-Huei Tsai, a neuroscientist at the Massachusetts Institute of Technology in Cambridge, and a co-author of the study, “Every day they’re reliving it. Exposure to the memory through photos or virtual reality simulations of the traumatic event in a safe environment — part of a technique known as extinction therapy — can help to dull the pain, but people with severe PTSD tend to relapse.”
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“I think this is very exciting,” said neuroscientist Marie Monfils of the University of Texas at Austin. Dr. Monfil’s work, which has demonstrated in related studies that briefly re-exposing an animal to the sound linked to a painful memory just once before extinction therapy begins, also enhances treatment — a finding that corresponds with the MIT research. Monfils also notes that other studies have shown that humans also reconsolidate memories. “The more treatment avenues clinicians have at their disposition, the better equipped they will be to help a broader range of people.”
Tsai and colleagues at MIT have been able to simulate the disorder by delivering electrical shocks to the feet of mice while playing a loud sound. The mice learned to associate the painful stimulus with the loud sound such that they would freeze whenever they heard the sound even though they didn’t receive an electrical shock to their feet. One day after the fear-conditioning, researchers repeatedly played the sound in a safe environment, to make the mice forget the fearful association. However, when extinction therapy was started 30 days later, the researchers found that the therapy didn’t work. The reason for this is in part that the memory had become epigenetically ingrained.
Tsai notes, with mice, a traumatic memory takes about a week to be permanently written into the epigenome. However, her work suggests that there are a class of drugs known as histone deacetylase inhibitors (HDACi) that have the ability to clear epigenetic markers from DNA that can lengthen that window.
In the current study, mice were given HDACi before they began extinction therapy and the drug appeared to prime the epigenome, creating a short period in which memories could be consolidated or modified. The researchers report that the HDACi alone had no effect on the rodent memory, however one dose combined with extinction therapy made the mice stop freezing when they received the traumatic sound.
Although HDACis are approved as cancer drugs, Tsai feels that it may be some time before this approach could be applied to patients with PTSD. However, she feels that a short exposure to an HDACi would be sufficient for successful PTSD treatment. At this time, it is not clear how specific memory alterations would be or how broad the effects are on the brain. Tsai also notes, HDACis appear to prime the brain’s epigenome for any sort of alteration which suggests that the stimulus used to extinguish a memory may need to be specific to the original experience. Earlier work by Tsai and colleagues has demonstrated that these drugs can be used to enhance memories in mouse models of Alzheimer’s disease.
Currently, Tsai and coworkers are trying to determine which genes are affected by the fear memory as well as understand how these genes act in the brain’s hippocampus. The hippocampus is were memories are stored and its cortex is where meanings are assigned to them.