TLR7-mediated inflammation and behavior

ABSTRACT

Methods: Here, we sought to investigate the effects of TLR7 pathway activation on mouse behaviour 24 hours post-activation. Female CD1 mice received an intraperitoneal injection of the synthetic TLR7 agonist, R848, or an equivalent volume of saline and were subjected to the Open Field and Forced Swim Test 24 hours later (n=10/group). Brain and liver tissues were then collected for downstream gene expression analysis. Result(s) Independent T-tests confirmed that systemic R848 challenge induced a strong peripheral and central inflammatory response, as indicated by a 250-fold increase in hepatic SAA-2 mRNA expression (p<0.0001) and a 75-fold increase in CXCL10 mRNA expression in the prefrontal cortex (p<0.01), relative to controls. These changes in inflammatory markers were accompanied by evidence of sickness behaviour - in particular, a decrease in exploratory rearing (p<0.01). Conclusion(s) This demonstrates that R848 can be used to create a model reflective of viral-like illness and provides a useful tool for investigating the behavioural effects of TLR7-mediated inflammation. To further these results, we aim to explore the metabolic consequences of LPS and R848 challenge and relate these to inflammatory and behavioural changes. This will accompany our data on the metabolic signatures of SARS-CoV-2-infected cells and animals, and of long-COVID patients. Copyright © 2022