TLR7-induced murine inflammation results in a global neuroinflammatory response driving neural circuit-specific transcriptomic changes.

Interactions between the brain and immune system play a key role in the aetiology of brain disorders, with inflammation emerging as a potential causal factor in subsets of major depressive disorder, particularly those resistant to treatment. The mechanisms through which immune activation might drive depressive symptoms remain elusive, limiting the ability to develop new targeted therapies. Using a mouse model of neuroinflammation, involving a TLR7/8 agonist, we combined whole-brain and spatial transcriptomics approaches to determine whether TLR7/8-driven neuroinflammation resulted in consistent immune and neurobiological transcriptional changes throughout the brain. We found evidence of strong immune activation throughout the brain,. and this global inflammatory signal led to regionally specific changes in gene expression. In particular, we found reduced expression of genes associated with synaptic function in brain areas underlying mood and anxiety, such as ventral striatum and amygdala.