Exercise stimulates neuron growth and helps you forget trauma and addictions

Researchers from the University of Toronto, Canada, and Kyushu University, Japan, have found that increasing the production of neurons and subsequent rewiring of neural circuits in the hippocampus through exercise or genetic manipulation helps mice forget traumatic or drug-related memories. These findings, published in the journal Molecular Psychiatry, may 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 attack. Globally, about 3.9% of the population suffers from PTSD, which is characterized by vivid flashbacks and avoidance of places or people that remind them of the traumatic event. Currently, PTSD is 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 mouse study, 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 memories of fear. The hippocampus, an area of the brain important for forming memories associated with specific places and contexts, produces new neurons every day in an area called the dentate gyrus.

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

The researchers gave mice two strong shocks under different conditions. First, the mice were given an electric shock after they left a brightly lit white box and entered a dark compartment that smelled of ethanol. After the second shock in a different environment, 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 spread to other dark compartments, showing a generalized fear. In addition, the mice explored open spaces less and avoided the center, which indicates anxiety.

The researchers then examined whether these PTSD symptoms could be alleviated through exercise, which studies have shown increases neurogenesis. The mice exposed to the double shock were divided into two groups: one group was given a running wheel.

After four weeks, these mice had an increase in the number of newly formed neurons in the hippocampus, and, importantly, symptoms of PTSD were less severe compared to mice without access to the running wheel.

In addition, when mice were able to exercise before the second shock, it also prevented the development of some PTSD symptoms.

However, because exercise affects the brain and body in a variety of ways, it was not clear whether this is due to rewiring of hippocampal neural circuits through neurogenesis or other factors. Therefore, the researchers used two different genetic approaches to evaluate the effect of integrating newly formed neurons into the hippocampus exclusively.

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, in which they added light-sensitive proteins to newly formed dentate gyrus neurons, allowing the neurons to be activated by light. When they shined blue light on these cells, new neurons matured faster. After 14 days, the neurons grew 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 the growth of neurons. This also led to faster growth of neurons and increased inclusion in 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 of exercise and did not reduce anxiety levels in mice.