Early childhood cold could be to blame for learning disorders

Frequent respiratory virus in animal experiments has consequences in brain and behavior

Respiratory Syncytial Virus (RSV) © CDC
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A seemingly harmless cold in infants and young children could be responsible for later learning disorders of the children. Because the triggering virus also reaches the brain and can trigger cognitive deficits there, as experiments with rats and mice now suggest. It is therefore urgent to develop effective and safe Respiratory Syncytial Virus (RSV) vaccines, Chilean researchers warn in the journal Proceedings of the National Academy of Sciences.

Hardly a child escapes these viruses: 70 percent of all infants in the first year of life and almost 100 percent in the second have at least one infection with the so-called respiratory syncytial virus (RSV) behind them. "Respiratory syncytial virus is the leading cause of respiratory disease in infants worldwide, " said Janyra Espinoza of the Catholic University of Chile in Santiago and her colleagues. Typically, a feverish cold, bronchitis, sometimes respiratory distress to the point of pneumonia the result. The infection usually heals without consequences - so at least that's what they thought.

But recently, reports of neurological side effects have increased. Cramps, dysphagia, lethargy, paralysis, respiratory arrest, or encephalopathy - pathological changes in the brain - occur in around two percent of cases. However, how the virus triggers these neurological symptoms, how it gets into the brain and what the consequences are has remained unclear, the researchers say.

Three days to the brain stem

To first track the path of viruses in the body, Espinoza and her colleagues infected rats and mice with RSV by trickling a virus solution into their nostrils. The following days, the animals were sampled at regular intervals and blood samples, as well as samples of various body tissues, including lung, nose and brain were taken and examined for viral RNA and virus proteins.

The result: 24 hours after infection, the virus had reached the olfactory bulb, on the third day, the researchers found viral traces already in several areas of the brain. After a week, the pathogen could be detected in the brain stem. "This is an important find, because the rapid infection of the brain stem could explain why in some RSV-affected children, respiratory arrest occur, " the researchers explain. display

As it turned out, however, the viruses not only reach the olfactory nerves, but also a second way into the brain: they use cells of the immune system as Trojan horses. Traveling piggyback on these cells, they can pass through the blood-brain barrier unhindered. When the researchers administered an antibody to the infected animals that paralyzed the immune cells, the viral load in the brain also dropped significantly, they report.

Marbles in the litter and platform underwater

But how does the infestation of the brain affect RSV? To find out, Espinoza and her colleagues left the rats and mice one month after their infection in two different behavioral and learning tests against uninfected conspecifics. In the first, the researchers placed several marbles on the litter box and stopped the time the animals needed until they had buried all the marbles - which corresponds to their natural behavior. The infected rodents performed much worse than healthy control animals, as the scientists report.

In a second experiment, infected and uninfected rats had to find a submerged platform and remember their position. There were also marked differences: RSV-infected rats need much longer to learn where the hidden platform is located, they even paddled for longer than others, even after several passes control animals. Further analysis revealed that the virus interferes with synaptic functions in an important brain area for learning - the hippocampus.

Protection of children from consequences is important

"Our findings indicate that the virus causes long-lasting disturbances of both instinctive action and learning, " the researchers note. To be sure, they only found their finds in rats and mice. However, in their view, this does mean that it is important to find a vaccine that will protect children from such consequences as quickly as possible. One candidate for this has already been tested by Espinoza and her colleagues on their experimental mice. It is a genetically modified variant of the tuberculosis vaccine BCG, which contains proteins of the RS virus.

When scientists inoculated their mice with RSV infection with this vaccine, they had significantly lower levels of virus in the lungs and brain. They also performed as well in the learning and behavioral tests as healthy control mice. This shows that immunization with this vaccine both protects against the disease and against the virus-related consequences in the brain, the researchers note. (Proceedings of the National Academy of Sciences (PNAS), 2013;, doi: 10.1073 / pnas.1217508110)

(PNAS, 07.05.2013 - NPO)