In a study published in Nature Medicine, investigators found that when a virus enters the bloodstream it activates the first responder immune cells, CX3CR1highLY6Clow monocytes.
The body’s immune response to viruses such as HIV and influenza may cause learning and memory problems, according to the results of a recently-published study.
The activation of the immune system has long been linked to cognitive issues, but the mechanisms behind it have been unclear.
In a study published in Nature Medicine, investigators found that when a virus enters the bloodstream it activates the first responder immune cells, CX3CR1highLY6Clow monocytes. These monocytes release the TNF-α protein, which then migrates to the brain and blocks the formation of nerve cell connections.
In mouse models, this loss of connections between nerve cells within the brain prevented the nerve cells from turning sensory information into memories. As a result, the mice did worse on tests that examined learning abilities.
These changes in nerve connections were triggered in the periphery rather than the brain, where the viral infection first contacts CX3CR1highLY6Clow monocytes in the bloodstream, according to the authors.
“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,” said author Guang Yang, PhD. “Our results suggest that existing anti-inflammatory treatments that target TNF-α may protect against brain dysfunction during peripheral infection.”
During the study, investigators found that exposure to a mimic (mimetic) of viral infection called poly(I:C) eliminated more than twice the percentage of dendritic spines compared with mice whose immune systems were not activated. These findings suggest a disruption of synaptic networks. Additionally, mice trained to run on a rotating rod formed significant less dendritic spines when exposed to poly(I:C).
The investigators also measured the levels of cytokines in mice at several time points following the injection of poly(I:C). The results showed a larger and longer-lasting increase in levels of TNF-α than in other cytokines.
Guang and his team hypothesized that the impact of systemic immune response on nerve cell connections was executed via TNF-α signaling. Mice engineered to lack TNF-α signaling in white blood cells did not experience a decrease in dendritic spine formation or in motor learning ability when exposed to the viral mimetic.
In the future, the investigators plan to seek out drugs or treatments that specifically target CX3CR1highLY6Clow monocytes to prevent these signals to the brain after infection. Furthermore, Guang may examine whether existing anti-TNF drugs could be used to prevent these cognitive issues.