A team of neuroscientists from the Massachusetts Institute of Technology (MIT) has discovered a drug treatment that may soon help people who suffer from post-traumatic stress disorder (PTSD). The researchers used the treatment, known as histone deacetylase (HDAC) inhibitor, on mice and found it helped them overcome stressful memories.
In the study published in the January 16 issue of the journal Cell, the researchers instilled traumatic memories in mice by giving them weak electric shock when they enter a specific chamber. The researchers found that the mice overcome their fears when they are placed in the same chamber again without giving them electric shock but only if their traumatic memory was 24 hours old.
The researchers observed that chromatin, which is consist of DNA and proteins that make up the cell's nucleus, undergoes extensive modifications when the mice were reconditioned i.e. placed back in the feared chamber without giving them electric shock. The researchers also found that a process called histone acetylation of memory-related genes caused by inactivation of the protein HDAC2 and which could activate processes to form new memories or rewrite old ones, occurred in the mice.
Histone acetylation, however, did not occur on mice with 30 days old memory of the electric shock so the researchers gave them HDAC2 inhibitor shortly after reconditioning and found that the stressful memories were extinguished as easily as in the mice with 24-hour memories.
The researchers found that the HDAC2 inhibitor treatment can turn on immediate early genes, which activate other genes needed for memory formation as well as result in an increase in the number of connections among neurons in the brain's hippocampus, where memories are formed.
"By inhibiting HDAC2 activity, we can drive dramatic structural changes in the brain. What happens is the brain becomes more plastic, more capable of forming very strong new memories that will override the old fearful memories," said study senior author and director of MIT's Picower Institute for Learning and Memory, Li-Huei Tsai.
Still, the researchers acknowledged that older memories are difficult to overcome even with the help of the drug. "If you do something within this window of time, then you have the possibility of modifying the memory or forming a new trace of memory that actually instructs the animal that this is not such a dangerous place," Tsai said. "However, the older the memory is, the harder it is to really change that memory. Our experiments really strongly argue that either the old memories are permanently being modified, or a new much more potent memory is formed that completely overwrites the old memory."
The researchers used HDAC only on mice so they do not know yet if it could be effective in treating people with PTSD but if the drug does work on humans, its potentials could go far beyond PTSD, opined Kerry Ressler, a psychiatrist at Emory University in Atlanta.
"The basic idea of exposure therapy holds across a number of anxiety and fear-related disorders, including PTSD, panic disorder, and phobias like fear of heights, where fear memories are often more remote," Ressler said. "Combining psychotherapy with a drug that augments memory retrieval could access these deeply buried fear memories, while also reducing the number of sessions a patient needs to eliminate their anxiety."
To date, one of the most common methods of treating PTSD patients is through behavioral therapy, which encourages patients to face traumatic memories and replace them with non-stressful ones. The method, however, does not work all the times.
