Exercise stimulates neuronal growth and helps you forget trauma and addictions

Researchers from the University of Toronto, Canada, and Kyushu University, Japan, have found that increasing the formation of neurons and then rewiring neural circuits in the hippocampus through exercise or genetic manipulation helps mice forget traumatic or drug-related memories. The findings, published in the journal Molecular Psychiatry, could offer a new approach to treating mental disorders such as post-traumatic stress disorder (PTSD) or drug addiction.

PTSD is a mental disorder that can be caused by experiencing or witnessing a traumatic event, such as a natural disaster, serious accident, or assault. Worldwide, about 3.9% of the population suffers from PTSD, which is characterized by vivid memories and avoidance of places or people that remind them of the traumatic event. PTSD is now often treated with therapy or medications such as antidepressants, but because many people do not respond effectively to treatment, researchers continue to look for different treatments.

In this study in mice, Associate Professor Risako Fujikawa from the Faculty of Pharmaceutical Sciences at Kyushu University, her former supervisor Professor Paul Frankland from the University of Toronto and their team, including Adam Ramsaran, focused on how neurogenesis – the process of forming new neurons – in the hippocampus affects the ability to forget fear memories. The hippocampus, a brain region important for forming memories associated with specific places and contexts, produces new neurons daily in a region called the dentate gyrus.

"Nurogenesis is important for forming new memories, but also for forgetting them. We think this happens because when new neurons integrate into neural circuits, new connections are formed and old ones are destroyed, impairing the ability to recall memories," Fujikawa explains. "We wanted to see if this process could help mice forget stronger, traumatic memories."

The researchers gave mice two strong shocks in different conditions. First, the mice were shocked after they left a brightly lit white box and entered a dark compartment smelling of ethanol. After a second shock in a different setting, the mice exhibited PTSD-like behavior.

A month later, the mice were still fearful and reluctant to enter the original dark compartment, indicating that they had not forgotten the traumatic memory. This fear extended to other dark compartments, indicating generalized fear. In addition, the mice explored open spaces less and avoided the center, indicating anxiety.

The researchers then looked at whether these PTSD symptoms could be alleviated by exercise, which studies have shown increases neurogenesis. The mice that had been given the double shock were divided into two groups: One group was given a running wheel.

After four weeks, these mice had increased numbers of newly formed neurons in the hippocampus and, importantly, had less PTSD symptoms than mice without access to the running wheel.

Additionally, allowing the mice to exercise before the second stroke also prevented the development of some PTSD symptoms.

However, because exercise affects the brain and body in a variety of ways, it was unclear whether this was due to the rewiring of hippocampal neural circuits through neurogenesis or other factors. So the researchers used two different genetic approaches to assess the impact of the integration of newly formed neurons into the hippocampus alone.

When new neurons in the hippocampus were activated by light, they grew faster and showed more branching. Photo: Paul Frankland; University of Toronto. First, the researchers used a technique called optogenetics, which involves adding light-sensitive proteins to newly formed neurons in the dentate gyrus, allowing the neurons to be activated by light. When they shone blue light on these cells, the new neurons matured faster. After 14 days, the neurons had grown longer, had more branches, and were more quickly integrated into the neural circuits of the hippocampus.

In a second approach, the research team used genetic engineering to remove a protein in newly formed neurons that slows down the growth of neurons. This also led to faster growth of neurons and increased recruitment into neural circuits.

Both of these genetic approaches reduced PTSD symptoms in mice after a double shock and shortened the time it took to forget a fear memory. However, the effect was weaker than that seen with exercise and did not reduce the mice's anxiety levels.