How can you stop old anxieties from resurfacing? An injection of new neurons may help, a study in mice suggests.
Post-traumatic stress disorder (PTSD), anxiety and other fear-related disorders are difficult to treat, and many people who seem to get better later relapse.
A similar phenomenon occurs in rodents. Adult mice can be conditioned to fear a sound by giving them an electric shock every time they hear it. Playing the sound repeatedly without the shock gradually wipes out the fear – a process known as extinction training. However, the fear often returns spontaneously if the mouse hears the sound later on.
Baby mice, on the other hand, do not seem to relapse as much. Yong-Chun Yu at Fudan University in China and his colleagues wanted to know if they could treat fearful adult mice with brain cells from mouse embryos.
The transplants did not prevent the mice developing new fears, nor help them overcome existing ones – at least not by themselves. But coupled with extinction training, the embryonic cells did help wipe out existing fears and prevent the mice relapsing.
Targeting the fear centre
First, the researchers injected live brain cells from mouse embryos into the amygdalae of adult mice – the parts of the brain involved in fear. Other mice were implanted with dead embryonic brain cells as a comparison.
Two weeks after transplantation, the mice were conditioned to fear a sound, freezing whenever they heard it. The mice stopped being afraid after two days of extinction training. A week later, the mice were played the same sound to see if their fear would come back. The team found that the fear response was three times less likely to return in the mice that had received a transplant of live embryonic neurons.
In a separate experiment they tested whether embryonic brain cells could erase bad memories altogether. Mice were conditioned to fear a sound before receiving the transplant. When they heard the sound afterwards they still froze, suggesting the memory had not been removed. However, they were significantly more responsive to extinction training.
Further analyses showed that the transplant turned mature amygdalae back to a juvenile stage. How this rejuvenation process helps conquer fear is unclear, and the team don’t know yet how long the effect lasts.
The team hope to develop their findings into a treatment for PTSD and anxiety in people.
Elena Bagley at the University of Sydney, Australia, says it’s an interesting idea but there are hurdles. One is the risk that the body receiving the transplant might reject the cells, or that the implanted cells could also affect other functions.
“The amygdala is involved in many types of associative learning that are really important for decision making, so I would be concerned about the effects of promoting this juvenile-like amygdala on those other aspects,” says Bagley.
Nevertheless, Yu says, “our results are an encouraging step towards using neuron transplantation” to prevent pathological fears that don’t respond to extinction therapy, something that has never been tried before.
Journal reference: Neuron, DOI: 10.1016/j.neuron.2016.11.018