# Forty-eight divers worked underwater for 30 minutes, one hour or three hours and only the longest exposure raised anxiety while rat experiments linked cognitive decline to CCR3-driven brain inflammation

> Three hours of underwater work left a small group of professional divers with lower memory and processing-speed scores, while shorter sessions produced different results. Follow-up experiments in rats linked the decline to inflammation in a memory center of the brain. Researchers then...

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Published: 2026-08-18T03:30:02+00:00
Categories: Explainer, Health

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Three hours of underwater work left a small group of professional divers with lower memory and processing-speed scores, while shorter sessions produced different results. Follow-up experiments in rats linked the decline to inflammation in a memory center of the brain. Researchers then reduced the activity of one gene, CCR3 and the animals performed better in memory tests after prolonged underwater exercise.

The findings come from an [iScience study](https://doi.org/10.1016/j.isci.2024.110379) led by researchers associated with the **Naval Medical University** and the Navy Special Medical Center in Shanghai. The work combined observations in human divers with controlled animal experiments, allowing the team to examine changes that could not be measured directly inside a diver's brain.

CCR3 may help control how immune cells in the brain respond to prolonged physical stress. Its role in the rat experiments offers an early clue for protecting **cognitive performance** during long underwater missions, although the technique used in the animals is far from ready for people.

## Long underwater sessions slowed divers' thinking

The human part of the study involved 48 male **special operation divers** between ages 18 and 32. They had between two and 12 years of diving experience. Researchers divided them into groups that worked at a depth of about 10 meters for 30 minutes, one hour, or three hours.

Each diver completed tests before and after his session. Saliva samples were used to measure cortisol, a hormone that rises during stress. Memory tests asked participants to remember animals while solving simple math problems. Another task measured processing speed by asking divers to compare symbols under a time limit. The [published record](https://pubmed.ncbi.nlm.nih.gov/39156650/) describes the study groups and the main cognitive results.

Cortisol rose after every session, which showed that underwater work placed the body under acute stress even at the shortest duration. Cognitive scores improved after the 30-minute operation and remained broadly stable after one hour. Following three hours underwater, memory and processing-speed scores fell and anxiety scores increased.

The pattern resembles a curve often seen in exercise research. A moderate challenge can increase alertness for a time, while a longer workload can strain the brain and body. Group sizes were small, with 20 divers in the 30-minute group, 15 in the one-hour group and 13 in the three-hour group, so larger trials will be needed to define a safe time limit.

## Rat tests traced changes inside the brain

Human tests can show when thinking changes, yet they cannot easily reveal activity inside brain tissue. The researchers therefore placed rats in a chamber that simulated an underwater pressure of two atmospheres. The animals swam without added weights for periods ranging from 30 minutes to three hours.

Blood tests showed that the rats experienced a stress response. Animals exposed for longer periods also displayed more anxious behavior in an open arena. The team then used the **Morris water maze**, a standard experiment in which a rat learns the location of a hidden platform in a pool.

Rats that completed the longer underwater exercise sessions crossed the former platform location fewer times during the memory test. They also spent less time in the part of the pool where the platform had been. Their swimming speeds remained similar, which helped the researchers separate memory performance from basic movement ability. Full experimental details appear in the [open-access paper](https://pmc.ncbi.nlm.nih.gov/articles/PMC11326909/).

The rat and human results followed a similar general direction as exposure length increased. Differences appeared in the timing, since the animals showed clear problems after shorter exposures than the divers. Species respond differently to pressure and physical strain and the rat chamber reproduced only selected parts of a real underwater mission.

## Inflammation rose as exposure time increased

Researchers next examined the **hippocampus**, a brain region needed for learning and memory. Tissue staining showed limited structural injury after a single exercise session. Several signs of healthy brain function still changed after the longer exposures, even without widespread loss of nerve cells.

Levels of two proteins called **BDNF and TrkB** fell in rats that completed the two-hour and three-hour sessions. BDNF helps nerve cells survive and supports the connections involved in learning. TrkB is a receptor that allows cells to respond to BDNF. Lower activity in this system can signal reduced support for memory-related brain circuits.

Immune cells called **microglia** also became more active in the hippocampus. Microglia patrol brain tissue and respond to injury, infection, or stressful changes in their surroundings. A strong response can release chemical signals that interfere with nearby nerve cells.

The longer sessions raised levels of inflammatory chemicals including IL-1 beta, IL-6 and TNF-alpha. Researchers use the term **neuroinflammation** for this kind of immune activity inside the nervous system. The study abstract summarizes the finding: "Prolonged exposure elicits significant cognitive impairment and hippocampal dysfunction, accompanied by increased neuroinflammation."

## RNA sequencing singled out CCR3

With signs of inflammation established, the team searched for genes whose activity changed after three hours of underwater exercise. The researchers used **RNA sequencing** to compare hippocampal tissue from exposed rats with tissue from animals in the normal control group.

The analysis identified 395 genes with significant changes under the study's screening rules. Activity increased in 246 genes and decreased in 149. Many of the differences involved immune communication, responses to stress hormones and interactions between cells and their surroundings.

One gene drew particular attention. **CCR3** carried the largest change among 11 genes connected with a pathway that helps cells exchange inflammatory signals. The receptor produced by CCR3 can detect chemical messengers called chemokines, which help guide immune responses. The study's [RNA sequencing data](https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE247651) are publicly available through the National Center for Biotechnology Information.

Additional tests showed that CCR3 activity rose in the hippocampus after prolonged underwater exercise. Tissue images placed much of the increased receptor activity in microglia, with smaller amounts seen in neurons and other support cells. The findings gave the researchers a specific target for the next experiment.

## Silencing CCR3 improved memory in rats

The team used an **adeno-associated virus** to carry a short genetic instruction into both sides of the rat hippocampus. The instruction reduced production of CCR3. A control group received a similar virus that lacked the active CCR3-silencing sequence.

Three weeks after injection, laboratory tests confirmed lower CCR3 messenger RNA and protein levels in the treated animals. The rats then completed three hours of underwater exercise before taking the water-maze memory test.

Animals with reduced CCR3 crossed the former platform location more often and spent more time in the target area than exposed rats in the control treatment group. Levels of BDNF and TrkB also recovered, suggesting that memory-related signaling in the hippocampus had improved.

The experiment provides evidence that CCR3 helped drive the cognitive problems seen in the rat model. It also went beyond a simple association, since changing CCR3 activity altered the outcome. The evidence remains tied to a highly controlled animal experiment involving direct delivery of genetic material into the brain.

## Microglia shifted toward a protective state

Lowering CCR3 did not greatly reduce the total number of activated microglia. Instead, markers associated with the cells' behavior changed. The treated animals had lower levels of iNOS, a marker linked with inflammatory activity and higher levels of Arg-1, which is associated with tissue protection and repair.

Microglia can take on a wide range of states depending on signals from nearby cells. The study describes the shift using two broad categories, an inflammatory M1 state and a protective M2 state. Modern research often finds many overlapping states between those categories, so the markers offer a simplified view of a complex process.

In the researchers' interpretation, reduced CCR3 encouraged activated microglia to release fewer damaging inflammatory signals while supporting a more protective environment. Levels of IL-1 beta, IL-6 and TNF-alpha fell after CCR3 knockdown. BDNF signaling also improved, providing a possible bridge between the immune response and better memory performance.

The mechanism could explain why the animals improved even though microglia remained active. Brain immune cells still responded to the prolonged exercise, while the type of response changed. A calmer chemical environment may have allowed hippocampal nerve circuits to function more effectively.

## What the findings could mean for divers

Long underwater missions can combine pressure, physical effort, restricted movement, cold and mental strain. Divers may also need to manage equipment or complete careful tasks while visibility is poor. A decline in processing speed or memory could raise the chance of an operational mistake.

The study suggests that mission duration deserves close attention alongside depth and breathing conditions. Thirty minutes of work was followed by improved scores in the human group, while three hours was followed by poorer scores. The experiment cannot establish a universal limit because each duration involved a separate, relatively small group.

CCR3 offers researchers a possible route for future brain-protection studies. Existing medical research has examined the receptor in allergies and inflammatory disease and other animal studies have explored its role in age-related cognitive changes. Any future diving application would require a safe method that acts in the right cells without weakening useful immune defenses elsewhere in the body.

Practical protections may eventually combine biological research with mission planning. Work-rest schedules, close monitoring and limits suited to the dive environment could reduce strain before a drug or gene-based treatment is considered. The current results help identify biological warning signs that future studies can measure.

## Questions remain before human treatments

Several limits keep the findings at an early stage. The human trial included only young adult men who were experienced divers and identified as Han Chinese. Results could differ in women, older divers, trainees, or people with different health backgrounds. Each diver completed one assigned duration, leaving open questions about how the same individual would respond across several mission lengths.

The rat model added firm control over pressure and exercise time, yet real dives include many changing conditions. Water temperature, depth, breathing gas, workload, sleep and repeated exposure could influence cognitive performance. The study focused mainly on duration and the authors call for animal models that examine other parts of the underwater environment.

Direct viral injection into the hippocampus is an invasive research method. Human use would demand years of safety work and a delivery approach suited to clinical care. Researchers would also need to determine whether CCR3 changes cause similar effects in the human brain during prolonged underwater operations.

CCR3 appeared mainly in microglia in the rat hippocampus, although neurons and other brain cells also carried some of the receptor. Future experiments can target specific cell types and map the steps between CCR3 activity, inflammatory signals and memory loss. The [journal article](https://www.sciencedirect.com/science/article/pii/S2589004224016043) also notes that the detailed molecular process remains unresolved.

The present evidence supports a focused conclusion: prolonged underwater exercise can strain cognition and CCR3 helped control the inflammatory response in rats. Larger human studies and more realistic dive models will determine whether the same pathway can guide safer long-duration operations.