Fri. Mar 31st, 2023
The body's defenses against common viruses can confuse neurons, cause depression

Getting sick is of course a setback. But besides making us feel nauseous and stuck in bed, viral infections can actually make us depressed. While scientists have known about this connection for some time, there has been little data on how everyday viral infections, such as the flu, can affect our moods.

Now data from a new mouse study show that common viruses can fuel sadness by causing the cells along the blood-brain barrier to release signals that silence the chatter between neurons in the region of the brain responsible for mood. The findings, published this week in the journal Immunitycould finally explain the link between infections and mental health problems, and it could point researchers to new strategies for treating depression and other mood disorders.

Researchers have been collecting clues about the link between mental health and infections for years. While it was first dismissed as people just being blue about getting sick, doctors now accept that there is a condition called “sickness behavior.” This condition is characterized by cognitive impairment, drowsiness, general malaise, and other depression-like symptoms in people with an infection. Additionally, in a 2013 Danish study, researchers found that people treated for a serious infection were 62 percent more likely to experience mood disorders. Perhaps related, those who had an autoimmune disease were 45 percent more likely to have such a mental health problem.

Researchers began to suspect that infections could cause the immune system in the brain to go berserk. Specifically, researchers hypothesized that illness behaviors might be triggered by immune signals called cytokines that somehow made their way to the brain and altered the activity of neurons. However, researchers didn’t know what those signals were or which cells emitted them.

Researchers in Germany, led by Marco Prinz of the University of Freiburg, began to unravel the mystery by noticing a similarity between illness behavior and depressive symptoms in people who take cytokines called type I interferons (IFNs) as part of cancer treatment. Viruses, the researchers realized, also lead to the release of type I IFNs.

To test the hypothesis that these cytokines can cause mood problems, the researcher began experimenting with mice, to see if they could induce and then change signs of depression in the rodents. They were tested for depression using a standard swim test method, which basically works by dropping the rodents into a container of water and measuring how long they frantically splash around trying to get out. Depressed mice give up faster.

Infecting normal mice with a common, mild virus made the mice depressed, the researchers found. Next, the researchers tried the swim test with genetically engineered mice whose brain cells couldn’t respond to type I IFNs. Still, the mice became depressed.

Going back to the drawing board, the researchers hypothesized that perhaps the cytokine didn’t actually get into the brain, but could instead pass signals through the blood-brain barrier. They then tried the depression test with mice designed so that the cells lining their brains’ surfaces and blood vessels could not respond to type I IFNs. When those mice were infected with the virus, they didn’t get depressed.

By monitoring the activity of those blood-brain barrier cells in normal mice, the researchers found that the cells were activated by type I IFNs and released another cytokine called CXCL10 directly into the brain. In the hippocampus of the brain (the area responsible for controlling mood), CXCL10 impeded the firing of neurons, silencing electrical pulses in that part of the brain.

While more work needs to be done to validate the results and determine whether they are relevant to human health, the authors hope that finding ways to block CXCL10 could lead to a treatment for certain mood disorders.

Immunity2016. DOI: 10.1016/j.immuni.2016.04.005 (About DOIs).

By akfire1

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