Exercise Facilitates Memory Erasure in PTSD

Summary: Increased neuron formation in the hippocampus, stimulated by exercise or genetic manipulation, helps mice forget traumatic or drug-associated memories. This process involves the rewiring of neural circuits, disrupting the recall of fear memories. These findings offer potential new approaches to treating mental health issues like PTSD and substance abuse.

Highlights:

• Exercise and genetic manipulation increase neuron formation in the hippocampus.
• Increased neurogenesis leads to rewiring of neural circuits and forgetting of fear memories.
• This discovery could lead to new treatments for PTSD and addiction.

Source: University of Kyushu

Researchers from the University of Toronto, Canada, and Kyushu University, Japan, found that increased neuron formation and subsequent rewiring of neural circuits in the hippocampus through exercise or manipulation genetics helped mice forget traumatic or drug-associated memories.

The results, reported on May 8 in Molecular Psychiatry, could offer a new approach to treating mental health problems like post-traumatic stress disorder (PTSD) or substance abuse.

PTSD is a mental health problem that can be triggered by experiencing or seeing a traumatic event, such as a natural disaster, serious accident or attack. Worldwide, about 3.9% of the general population suffers from PTSD, with symptoms including vivid flashbacks and avoidance behaviors, such as staying away from places or pushing away people who remind them of them. traumatic event.

Currently, PTSD is often treated with therapy or medications such as antidepressants, but because many people do not respond effectively to them, researchers are always looking for different treatments.

In this mouse study, Assistant Professor Risako Fujikawa of the Faculty of Pharmaceutical Sciences at Kyushu University, her former supervisor, Professor Paul Frankland of the University of Toronto, and their team members, including Adam Ramsaran , focused on how neurogenesis (the process of forming new neurons) in the hippocampus impacts the ability to forget fear memories.

The hippocampus, a brain region important for forming memories related to specific places and contexts, produces new neurons daily in an area called the dentate gyrus.

“Neurogenesis is important for forming new memories but also for forgetting memories. We think this happens because when new neurons integrate into neural circuits, new connections are forged and old connections are lost, disrupting the ability to recall memories,” says Fujikawa.

“We wanted to see if this process could also help mice forget stronger, traumatic memories.”

The researchers gave mice two powerful shocks in different contexts. First, mice were shocked after leaving a well-lit white box and entering a dark, ethanol-scented compartment. After the second shock in another distinct environment, the mice showed PTSD-like behaviors.

More than a month later, the mice were still fearful and reluctant to enter the original dark compartment, indicating that they could not forget the traumatic memory. This fear spread to other dark compartments, indicating widespread fear. Additionally, mice explored open spaces less and avoided the center, suggesting anxiety.

The researchers then investigated whether these PTSD-like behaviors could be alleviated by exercise, which studies have shown stimulated neurogenesis. The double-shocked mice were divided into two groups and one group received a running wheel.

Four weeks later, these mice had increased numbers of newly formed neurons in their hippocampi, and more importantly, the PTSD-like behaviors were less severe than those in the double-shocked mice without access to the wheels.

Additionally, when mice were free to exercise before the second shock, this also prevented the development of certain PTSD-like behaviors.

However, because exercise impacts the brain and body in different ways, it was unclear whether the effect of exercise was due to rewiring of the hippocampal circuit through neurogenesis or other causes. factors. The researchers therefore used two different genetic approaches to exclusively evaluate the impact of the integration of newborn neurons into the hippocampus.

First, the researchers used a technique called optogenetics, in which they added 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 more quickly. After 14 days, the neurons were longer, had more branches and integrated more quickly into the neural circuits of the hippocampus.

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

These two genetic approaches reduced PTSD-like symptoms in mice after double shock and shortened the time it took for mice to forget the fear memory. However, the researchers found that the effect was weaker than that observed with exercise and did not reduce the mice’s anxiety levels.

“It could be that neurogenesis and remodeling of hippocampal circuitry disrupts fear memory, but has less effect on mood or emotion,” Fujikawa suggests. “Exercise also has broader physiological effects, which may contribute to the better results seen.”

Finally, the research team explored whether increased neurogenesis and hippocampal remodeling could also help in other mental disorders in which memory plays an important role, such as substance use disorders. For people struggling with drug addiction, relapse often occurs when reminders, such as being in an environment similar to where the drug was used, trigger powerful cravings.

The researchers placed mice in a two-room cage. In one room, the mice were given saline and in the other room, cocaine. Subsequently, when given free access to both rooms, the mice spent more time in the room in which they had received cocaine.

However, when the researchers used exercise and genetic methods to stimulate neurogenesis and hippocampal remodeling, they found that the mice stopped showing a preference for the room where they had taken cocaine, which which suggests that they had forgotten the connection between the play and the drug. .

For future research, Risako plans to find a drug that can stimulate neurogenesis, or hippocampal remodeling, in hopes that it could be tested as a potential treatment for PTSD and drug addiction. However, she also stressed the importance of exercise.

“In our experiments, exercise had the most powerful impact on reducing PTSD symptoms and drug dependence in mice, and clinical studies in humans also show it is effective,” Risako explains.

“I think that’s the most important takeaway.”

About this exercise and PTSD research news

Author: Danielle Ellenby
Source: University of Kyushu
Contact: Danielle Ellenby – Kyushu University
Picture: Image is credited to Neuroscience News

Original research: Closed access.
“Neurogenesis-dependent remodeling of hippocampal circuits reduces PTSD-like behaviors in adult mice” by Risako Fujikawa et al. Molecular Psychiatry

Abstract

Neurogenesis-dependent hippocampal circuit remodeling reduces PTSD-like behaviors in adult mice

Posttraumatic stress disorder (PTSD) is a hypermnestic state that develops in a subset of individuals following exposure to severe trauma. Symptoms of PTSD are debilitating and include increased anxiety, abnormal threat generalization, and impaired extinction.

In developing treatment strategies for PTSD, preclinical studies in rodents have largely focused on interventions targeting post-encoding memory processes such as reconsolidation and extinction. Instead, we focus here on forgetting, another post-encoding process that regulates memory expression.

Using a dual-trauma mouse model for PTSD, we asked whether promoting neurogenesis-mediated forgetting could weaken trauma memories and behavioral phenotypes associated with PTSD.

In the dual trauma paradigm, consecutive aversive experiences lead to a constellation of behavioral phenotypes associated with PTSD, including increased anxiety-like behaviors, abnormal threat generalization, and impaired extinction.

We found that post-training interventions that increased hippocampal neurogenesis weakened the original traumatic memory and decreased these PTSD-relevant phenotypes.

These effects were observed using several methods to manipulate hippocampal neurogenesis, including interventions limited to neural progenitor cells that selectively promoted the integration of adult-generated granule cells into hippocampal circuits.

The same interventions also weakened place preference memories for cocaine, suggesting that promoting hippocampal neurogenesis may represent a broadly useful approach in hypermnestic conditions such as PTSD and substance use disorders.