New drug harnesses the effects of post-traumatic stress disorder (PTSD) and gives those suffering a clean slate. Researchers at the Massachusetts Institute of Technology examined a drug known as a HDAC2 inhibitor which helped mice overcome traumatic memories.
The team of neuroscientists, lead by neurobiologist Li-Huei Tsai, found that by inhibiting HDAC2 activity they could drive dramatic structural changing to the brain. What Tsai said happens is the brain becomes more “plastic” and therefore more capable of developing very strong new memories that will supersede the old fearful memories.
Psychotherapy is more effective when treating recent traumatic events but hasn’t been very effective at harnessing those from long ago. This new study shows that modifying the molecules that connect to our DNA can help squash painful memories in both cases.
The study offers a system explaining why it is difficult to rid the brain of older memories and shows that HDACs can aid psychotherapy in treating anxiety disorders such as PTSD.
Tsai said the older a memory is the harder it becomes to extinguish or change that memory. The experiments from the research team strongly argue that either a new much more potent memory is formed that completely rewrites the old memory or the old memories are permanently modified.
To address the older traumatic memories Tsai and her team of neuroscientists used a procedure for studying responses of fear associated with traumatic memories. The researchers, in the first phase, exposed mice to a tone followed by an electrical shock to the foot. Once the mice learned that these two events were associated they started to freeze in fear, even when they only heard the tone without the shock.
Using an extinction protocol the research team repeatedly presented the mice with a tone, minus the electric shock, to see if the mice could unlearn to associate the tone with the shock. Ultimately they wanted to see if the mice would stop freezing when they heard the tone by itself.
The test was found to be successful with the mice which were exposed to the tone-shock connection just one day prior. The team did not find the same success with the mice that formed the traumatic memory one month earlier. The researchers drafted the theory that epigenetic alteration of genes involved in memory and learning might be responsible for the weakened response of treatment for older memories.
This theory caused the research team to test whether a family of enzymes, called HDACs; which promote long-lasting activation of genes involved in memory and learning, could actually replace outdated traumatic memories with new ones.
The mice that were previously exposed to the tone-shock pairing, after having received HDACs learned to stop freezing after hearing the tone, even the mice that formed the traumatic memory one month prior.
Tsai reported that collectively the team’s finding suggest that exposure-based therapy does not effectively weaken older traumatic memories when used alone. However the team did find when it is combined with HDACs the effects of the exposure-based therapy substantially improved when treating the most enduring traumatic memories.
Jelena Radulovic, a psychiatrist and molecular pharmacologist at Northwestern University’s Feinberg School of Medicine in Chicago, said many studies have shown that epigenetic changes are basic to learning but Tsai’s research goes beyond this. Radulovic said Tsai’s work shows that HDAC2 obviously affects several genes important for reconsolidation updates, and as memories age, this mechanism fails.
This is the first study to alter older fears in an animal model, according to the authors of the study. Kerry Ressler, a psychiatrist at Emory University, said if these findings apply to humans, the potential uses of HDAC inhibitors would expand way beyond the realm of PTSD.
Ressler said combining psychotherapy with a drug that enhances memory retrieval could reduce the number of sessions a patient would need to eliminate their anxiety, while accessing these deeply buried fear-based memories.
People suffering from PTSD crave a clean slate more than anything else when it comes to their traumatic memories. A research team, led by Li-Huei Tsai, has uncovered a chemical modification that allows memories to be edited by reconsolidation and produce fear extinction during behavior therapy.
This new drug harnesses the effects of post-traumatic stress disorder and gives those suffering a memory make-over.
By: Cherese Jackson (Virginia)