Scientists have discovered why sport actually protects against depression

A team of scientists from Laval University (Canada) has discovered why regular exercise and an "enriched" environment - and more broadly, favourable socioeconomic conditions - can reduce the risk of depression. In experiments on laboratory animals, the researchers showed: in chronic social stress, exercise and an improved environment help maintain the integrity of the blood-brain barrier (BBB) in brain areas associated with emotion and mood regulation.

The work is published in the journal Nature Communications. The authors emphasise the key role of the Fgf2 protein in this defence mechanism and see it as a potential biomarker of mood disorders.

How stress 'breaks down' the brain's defences

The blood-brain barrier is a system of cellular "boundaries" that limits the entry of substances from the blood into the brain. One important element of this defence is the protein claudin-5: it "closes the gaps" between cells. If claudin-5 becomes smaller, the barrier loses its tightness.

Previously, a group led by Professor Caroline Menard showed that in mice chronic stress leads to a decrease in claudin-5, after which the brain more easily penetrate pro-inflammatory molecules - and appear anxiety and depressive manifestations. According to the authors, a similar claudin-5 deficiency was noted in the brains of depressed people.

What exercise and an "enriched environment" revealed

In the new study, scientists modelled chronic social stress in mice (they were regularly exposed to a dominant male) and divided the animals into three groups:

• "enriched environment" (shelters, toys, nesting materials),

• free access to the treadmill wheel,

• control group without additional conditions.

The result was noticeable: in the control group, in the stressed mice the level of claudin-5 dropped by about 50%, whereas in the animals with the wheel or in the enriched environment the loss was minimal or absent. At the same time, behavioural signs of anxiety and depression were also reduced.

Fgf2 protein as a "resilience factor"

Further analysis showed that the protective effect was associated with increased levels of Fgf2 in the brain. To test the cause-and-effect relationship, the researchers used viral vectors to "twist" the production of Fgf2 up or down.

• Mice with increased Fgf2 were less likely to avoid contact after stress and showed greater resilience.

• When Fgf2 was decreased, the animals became more vulnerable to stress, were more likely to avoid social interaction and benefited less from exercise.

A possible biomarker of depression by blood test

Fgf2 has another important feature: the protein can be detected in the blood, especially when the barrier is weakened. Therefore, the team tested whether Fgf2 could become a biomarker of depression (such markers, which really help diagnosis and choice of therapy, are still few in clinical practice).

To do this, the researchers analysed about 100 blood samples from a biobank in Montreal and compared Fgf2 levels in people with and without depression. According to their findings, Fgf2 concentrations increased with the severity of depression and were likely influenced by environmental factors - such as employment or education level. The next step is to see if Fgf2 can reflect response to treatment and be useful in other mental disorders, including schizophrenia.