How Viruses Might Cause Brain Changes & Learning Problems

Despite mounting scientific evidence that viruses can cause changes in learning and memory, the reasons have remained elusive.

In a new study, scientists reported finding that viruses affect the immune system in a way that results in loss of connections between nerve cells in mice brains and those mice performed worse on tests of learning ability.

"This study in animals resonates with what we see in the clinic, where patients with acute or chronic infectious diseases often have weaker performance on motor skills and experience memory decline," study co-author Guang Yang said in a press release.

The research, conducted by scientists at the New York University School of Medicine was published online May 15th in Nature Medicine.

How a Virus Uses the Immune System to Change the Brain

One route of entry for viruses into the body is through the blood. Even if a virus initially enters through the lungs (like the flu virus) or the genital tract (like HIV), the virus often ends up in the blood.

Experiments in mice conducted by the investigators found that the effects of a virus-like infection — created by injecting the mice with a non-pathogenic compound that the body reacts to as if it were an infection — on the brain started in the bloodstream.

They found that when a virus enters the bloodstream, it triggers the immune system to respond. The first cells that respond to fight the foreign invader are immune cells that go by the name CX3CR1highLY6Clow monocytes in mice — a very unique subset of white cells. In humans, they go by the name CX3CR1highCD14dimCD16+, but, they both are the patrolling cells of the immune system.

Dendrites are projections from the brain's neuron cells that carry information from another neuron into the dendrite cell's body. Some dendrites have small projections called dendritic spines that process information received through the senses into memories. The responding monocytes in the mice released tumor necrosis factor alpha (TNFa) — a protein involved in modulating immune responses — that then traveled to the brain. Once in the brain, the study team found that TNFa blocked the formation of dendritic spines.

How Viruses Might Cause Brain Changes & Learning Problems — Dendritic spines. *Image via PLoSONE*

To test effects of infection on the animals' ability to learn, mice were trained to run on an accelerating rotating rod, while the investigators took images of the dendrites in their brain. Two days after the researchers infected the mice with the viral mimic, they did significantly worse on the rotating rod manipulation they had learned just days before.

Brain images showed the mice with the virus-like infection had lost than half the percentage of dendritic spines as uninfected mice did and led the scientist to conclude that immune disruption of synaptic networks was the cause of the impaired learning process they observed.

The study authors said that the unique subset of monocytes, as well as TNFa, may present potential therapeutic targets for preventing infection-induced cognitive dysfunction.