September 19, 2013
Discovery Of Memory Loss Gene Could Help PTSD Patients
redOrbit Staff & Wire Reports - Your Universe Online
The discovery of a gene partially responsible for the loss of old memories could benefit people suffering from posttraumatic stress disorder (PTSD) by making it easier to replace fear-inducing recollections with more positive associations, researchers from the Massachusetts Institute of Technology (MIT) claim in a new study.
To demonstrate how memory extinction works, the researchers used the example of a student being bullied on his or her way home from school each day. If the encounter happened at the same spot each day, that spot would probably begin to trigger a fear reaction. However, if and when the bully moved away, that spot would become less and less associated with the bullying events over time – thanks in part to the Tet1 gene.
“Tet1 and other Tet proteins help regulate the modifications of DNA that determine whether a particular gene will be expressed or not,” Anne Trafton of the MIT News Office explained in a statement. “Tet proteins are very abundant in the brain, which made scientists suspect they might be involved in learning and memory.”
Tsai and her colleagues teamed with researchers from MIT biology professor Rudolf Jaenisch’s laboratory at the Whitehead Institute to study mice that had their Tet1 gene made inoperative (or “knocked out”). They found that those mice were able to form new memories and learn new tasks as usual, but a series of experiments found they were unable to forget fear-causing memories.
The researchers conditioned the rodents to be afraid of a specific cage in which they would receive a mild shock. Once the memory was formed, the mice were placed in the cage but the shock was not administered. After a while, the mice with normal Tet1 levels lost their fear of the cage, but those lacking the gene remained fearful.
“What happens during memory extinction is not erasure of the original memory,” Tsai explained. “The old trace of memory is telling the mice that this place is dangerous. But the new memory informs the mice that this place is actually safe. There are two choices of memory that are competing with each other.”
That process is what occurs in normal creatures. However, mice without Tet1 “don’t relearn properly,” Rudenko said. “They’re kind of getting stuck and cannot extinguish the old memory.” Their findings were reinforced in a second set of experiments in which mice lacking the gene were able to learn how to navigate a water maze, but could not extinguish the memory of how to traverse the maze later on.
The researchers found that Tet1 exerts its effects on memory by altering DNA methylation levels, a modification which controls access to genes. Higher methylation levels block the promoter regions of genes and prevent them from being activated, they said, while lower levels permit them to be expressed. The study was funded by the National Institutes of Health, the Simons Foundation and the Howard Hughes Medical Institute.
“By demonstrating some of the ways that regulatory genes are methylated in response to Tet1 knockout and behavioral experience, the authors have taken an important step in identifying potential pharmacological treatment targets for disorders such as PTSD and addiction,” said Matthew Lattal, an associate professor of behavioral neuroscience at Oregon Health and Science University. Lattal was not a member of the research team.