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

Lindsay T Michalovicz1, Brent Lally1, Gregory W Konat1

  • 1Department of Neurobiology and Anatomy, West Virginia University School of Medicine, 1 Medical Center Dr., Morgantown, WV 26506-9128, USA.

Journal of Neuroimmunology
|July 23, 2015
PubMed

Insights

Viral mimetics like polyinosinic-polycytidylic acid (PIC) trigger brain hyperexcitability. This study reveals PIC activates the complement pathway, particularly complement factor B (CfB), in the hippocampus, suggesting a role in this neurological response.

Area of Science:

  • Neuroscience
  • Immunology
  • Genetics

Background:

  • Peripheral viral challenges can impact central nervous system function.
  • Hippocampal hyperexcitability is a hallmark of various neurological disorders.
  • Polyinosinic-polycytidylic acid (PIC) is a viral mimetic used to study immune responses.

Purpose of the Study:

  • To characterize the hippocampal genetic response to peripheral viral mimetic challenge.
  • To identify key molecular pathways involved in PIC-induced hyperexcitability.
  • To investigate the role of the complement system in this neurological response.

Main Methods:

  • Whole genome transcriptome analysis in mouse hippocampus.
  • Bioinformatic analysis of gene expression data.
  • Correlation of gene upregulation with observed hyperexcitability.

Main Results:

  • Peripheral PIC challenge caused temporal dysregulation of 625 hippocampal genes.
  • The complement pathway was the most significantly activated pathway.
  • Complement factor B (CfB) showed the highest gene response and its upregulation correlated with hyperexcitability.

Conclusions:

  • PIC-induced hippocampal hyperexcitability involves extensive genetic reprogramming.
  • The alternative complement cascade, particularly CfB, is implicated in mediating this response.
  • This suggests a link between innate immunity activation and neuronal excitability.
Keywords:
Complement systemHippocampusImmunofluorescenceInflammationPolyinosinic–polycytidylic acidTranscriptome

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