Peripheral challenge with a viral mimic upregulates expression of the complement genes in the hippocampus

- i.p. injection of a viral mimetic (PIC) induces hippocampal hyperexcitability.
- PIC challenge leads to extensive genomic reprogramming in the hippocampus.
- The complement pathway is significantly upregulated.
- The expression of complement factor B is commensurate with hyperexcitability.
- The alternative pathway may mediate hippocampal hyperexcitability.

Peripheral challenge with a viral mimetic, polyinosinic-polycytidylic acid (PIC) induces hippocampal hyperexcitability in mice. Here, we characterized this hippocampal response through a whole genome transcriptome analysis. Intraperitoneal injection of PIC resulted in temporal dysregulation of 625 genes in the hippocampus, indicating an extensive genetic reprogramming. The bioinformatics analysis of these genes revealed the complement pathway to be the most significantly activated. The gene encoding complement factor B (CfB) exhibited the highest response, and its upregulation was commensurate with the development of hyperexcitability. Collectively, these results suggest that the induction of hippocampal hyperexcitability may be mediated by the alternative complement cascades.