New discoveries suggest that cognitive problems caused by repeated mild head blows can be treated.

Neurological pathways that do not damage but have high-frequency effects on the brain blunt normal brain function and cause long-term problems in learning and memory have been identified. According to neuroscientists at Georgetown University Medical Center, this finding suggests that tailored medications can be designed and developed to reactivate and normalize cognitive function.

Researchers working with collaborators at the National Institutes of Health have previously discovered that rare mild head impacts do not affect learning and memory, but in their new study, 5 Reported on the 10th of March Nature CommunicationsResearchers have found that as the frequency of these undamaged head impacts increases, brain Adapt and change how it works. Researchers have discovered a molecular pathway responsible for this down-tuning of the brain that can prevent the development of this adaptation.

This study is the first to use mice to provide a detailed molecular analysis of what happens in the brain after a very repetitive and very gentle head blow. Animal modelDr. Mark Burns, Principal Investigator for the study, states that he is an associate professor in the Department of Neuroscience in Georgetown and head of the Institute for Brain Injury and Dementia.

“Most studies in this area have been done in more severe mouse models. Brain injuryIn the human brain, or with chronic traumatic encephalopathy (CTE), CTE is a degenerative brain disorder found in people with a history of recurrent head shock. “This means that we are only focusing on how the condition of CTE progresses. Our goal is, for example, the low level that many young soccer players regularly experience. It was to understand how the brain changes in response to the impact of the head. “

Researchers have found that the average high school and college football player is hit by 21 heads a week, while some professional players, such as the defensive end, are hit twice as hard. Behavioral problems that may be caused by head impact have been reported in athletes who have been repeatedly exposed to head impact.The problem is from mild learning and memory loss Behavioral changes This includes aggression, impulsivity and sleep disorders.

“These findings represent a message of hope for athletes and their families who are worried that behavioral and memory changes mean that CTEs are their future,” says Burns.

In this mouse study, researchers mimicked the mild head impact experienced by soccer players. Mice showed slow learning and impaired memory recall long after the head impact stopped. After the experiment, a detailed analysis of their brains showed no trauma to the brain or inflammation or tau pathology commonly found in the brains of people with CTE.

To understand the physiology underlying these memory changes, Bevan Main, Ph.D., co-lead author of the study and assistant professor of neuroscience in Georgetown. Performed RNA sequencing of the brain. “This type of analysis can point out a lot of things, such as energy usage and pathway problems like CTEs that are activated in nerve cells,” says Maine. “All our sequencing studies continued to point to the same thing: synapses that provide communication between neurons.”

The next step was to understand how synaptic function changed. Dr. Stephanie Slowley, a graduate of Georgetown’s interdisciplinary program of neuroscience and the first other co-author of the study, released a variety of neurotransmitters (chemicals that pass between neurons through synapses). We conducted electrophysiological studies on various neurons in charge of. “The brain was wired through synaptic channels, and these wires were found to be intact, but the method of communicating with glutamate was dull and suppressed,” Sloley said. I will.

Glutamate is the most abundant neurotransmitter in the brain and is found in more than 60% of brain synapses. It plays a role in synaptic plasticity. This is how the brain strengthens and weakens signals between neurons over time to shape learning and memory.

“Glutamate is usually very tightly controlled in the brain, but we know that head impact releases a burst of glutamate. The brain has repeated glutamate caused by high-frequency head impact. We believe that it adapts to bursts and weakens normal responses. Perhaps as a way to protect neurons, glutamate, “explains Slory. She found that there was a change in the way neurons detect and respond to glutamate release, which reduces their ability to learn new information.

With a single head hit or a rare hit, synapses do not go through this readjustment, Burns says. However, after only a week of frequent mild hits, glutamate detection remained slowed for at least a month after the effects had ended. Affected mice showed learning and memory deficiencies compared to animals in the placebo group.

The authors confirmed that cognitive changes were due to glutamate by administering to a group of mice a drug that blocks glutamate transmission before experiencing a series of head knocks. The drug is FDA approved for the treatment of Alzheimer’s disease. Despite being exposed to hits, these mice did not develop synaptic and neurotransmitter adaptations and did not develop cognitive problems.

“This is because the cognitive problems we see in mice that affect our heads are not due to irreparable brain damage or CTE, but to changes in the way the brain works. It shows, “says Main. “Not all athletes develop cognitive deficits, so it is very unlikely that young athletes will use such drugs as neuroprotective agents before playing sports,” he says. “Our findings are likely to be used to develop treatments that target synapses and reverse this condition. That work is already underway.”

Burns believes that CTE and this newly discovered mechanism are different. “I think CTE is a real concern for athletes exposed to head shocks, but I believe that newly discovered communication problems have nothing to do with CTE. Head shocks work the brain. Despite concerns that it could change, the study reveals that learning and memory loss after repetition: Head The effects do not automatically imply the future of untreatable neurodegenerative diseases. ”